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The Cell: Cell Junctions

Cell junctions are proteinaceous structures that physically hold 2 surfaces (cell-to-cell or cell-to-matrix) together. Cell junctions aid in communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence and structural support and act as a barrier. They are classified as occluding (tight junctions), anchoring (adherens, desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris and hemidesmosomes), and communicating (gap junctions). Type II hypersensitivity has been noticed with autoantibody production against the components of anchoring junctions, resulting in pathology such as pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris and bullous pemphigoid Bullous pemphigoid Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. Bullous Pemphigoid and Pemphigus Vulgaris.

Last updated: 21 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Tight Junctions

Defintion

Tight junctions (occluding junctions or zonula occludens) are intercellular adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies complexes composed of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis whose primary role is regulating the passage of water and solutes between epithelial cells ( paracellular Paracellular Renal Potassium Regulation permeability). 

Location

  • Found on the apical and basolateral sides of epithelial cells
  • Mainly present in gastric mucosa Gastric mucosa Lining of the stomach, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. The surface cells produce mucus that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the lamina propria at various region of the stomach (cardia; gastric fundus; and pylorus), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, hydrochloric acid, or hormones. Stomach: Anatomy, renal tubules, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology

Composition

Cell junctions are branching networks of sealing strands, each formed by multiple transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and associated intracellular proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.

Transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:

  • Embedded in the plasma membrane Plasma membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane of 2 adjacent cells: Extracellular domains of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis in 1 cell are continuous with those of transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis in the opposing cell.
  • Occludin proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis have extra- and intracellular loops that regulate paracellular Paracellular Renal Potassium Regulation permeability.
    • Influence intracellular activity such as gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression and energy metabolism
    • Have 9 major domains, which are distributed intra- and extracellularly
    • Stabilize tight junctions
    • Support the barrier function of tight junctions
  • Claudin proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are considered the backbone of tight junctions.
    • Seal paracellular Paracellular Renal Potassium Regulation space
    • 4 transmembrane domains, with both ends lying within the cytoplasm
    • Have the ability to bind BIND Hyperbilirubinemia of the Newborn to scaffolding proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Junctional adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies molecules regulate the paracellular Paracellular Renal Potassium Regulation pathway. 
    • Have only 1 transmembrane domain
    • Help maintain cell polarity
Types of cell junctions

Illustration depicting strands of transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (claudins and occludins) tightly binding adjacent plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membranes

Image: “Types of Cell Junctions” by OpenStax College. License: CC BY 3.0, edited by Lecturio.

Function

  • Diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis barrier between adjacent cells
  • Prevent passage of ions and molecules between cells
    • Molecules are selectively allowed based upon size and charge.
    • Generally, cations Cations Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. Electrolytes are preferentially allowed in transit.
  • Separate tissue compartments into apical and basal sides and maintain the polarity of cells
    • Prevent lateral diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis between the apical and basolateral surfaces
    • Preserve the functioning of specialized activities such as receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors-mediated endocytosis Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. The Cell: Cell Membrane
  • Maintain osmotic balance
  • Generally, cells are classified as being tight or leaky. Tight junctions have an important role in determining whether cells have tight or leaky epithelial cells.
    • Tight epithelial cells include distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome cells in the kidney and bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts and the cells composing the blood–brain barrier Blood–Brain Barrier Meningitis in Children ( BBB BBB Specialized non-fenestrated tightly-joined endothelial cells with tight junctions that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. Nervous System: Histology).
    • Leaky epithelial cells include cells in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System of the kidney. These cells contain fewer tight junctions, which contributes to their leakiness.

Anchoring Junctions

Adherens

Definition:

Adherens are junctions between cells that are linked to the actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton. These junctions are also known as zonula adherens, intermediate junctions, or belt desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris.

Location:

  • Between adjacent epithelial cells
  • Mainly seen in endothelial and epithelial cells
  • More basal than tight junctions

Composition:

  • Actin filaments Actin filaments Fibers composed of microfilament proteins, which are predominately actin. They are the smallest of the cytoskeletal filaments. The Cell: Cytosol and Cytoskeleton
  • E-cadherins
    • Transmembrane adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies protein
    • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes dependent
    • Form homodimers
  • Actin filaments Actin filaments Fibers composed of microfilament proteins, which are predominately actin. They are the smallest of the cytoskeletal filaments. The Cell: Cytosol and Cytoskeleton and E-cadherins are connected by vinculin and catenin. 
    • Catenins bind BIND Hyperbilirubinemia of the Newborn cadherin Cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer.
    • Catenins may also bind BIND Hyperbilirubinemia of the Newborn to the actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton.

Function:

  • Maintaining cells in a belt shape
  • Anchoring cells 
  • Providing strength
  • Maintaining cell shape (may serve a role in the actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction contractile ring)
Adherens junctions interact with actin filaments through its proteins such as cadherin and catenin.

Adherens junctions interact with actin filaments Actin filaments Fibers composed of microfilament proteins, which are predominately actin. They are the smallest of the cytoskeletal filaments. The Cell: Cytosol and Cytoskeleton through their proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, such as cadherin Cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer and catenin.

Image: “Principal interactions of structural proteins Structural proteins Proteins and Peptides at cadherin Cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer-based adherens junction” by Mariana Ruiz . License: Public Domain

Demosome

Definition:

Desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris are strong structures that assist in cellular adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies, tethering intermediate filaments Intermediate filaments Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. The Cell: Cytosol and Cytoskeleton to the plasma membrane Plasma membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane. These structures are also known as macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy adherens or spot desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris.

Location:

  • Located between adjacent cells
  • Found in epithelial cells, cardiomyocytes ( intercalated discs Intercalated discs Irregular, transverse, thick parts of the sarcolemma at the terminal ends of the cell branches. Muscle Tissue: Histology)
  • Generally, found in cells that are under large amounts of mechanical stress

Composition:

  • Desmosomal plaque Plaque Primary Skin Lesions:
    • Made of cadherin Cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
      • Desmoglein: a cellular adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies protein
      • Desmocollin: a cellular adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies protein
    • Located on the cytoplasmic side of the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane
  • Keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis intermediate filaments Intermediate filaments Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. The Cell: Cytosol and Cytoskeleton
  • Desmin filaments

Function:

  • Structural support
  • Maintains cell structure against mechanical force

Disease:

Several diseases are associated with desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris. Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types and blistering conditions have been linked with mutations in the desmosome family of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis

  • Arrhythmogenic cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types (CM)
  • Pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris
  • Pemphigus foliaceus
Desmosomes linking together adjacent cells

Desmosomes Desmosomes A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. Bullous Pemphigoid and Pemphigus Vulgaris linking together adjacent cells

Image by Lecturio.

Hemidesmosome

Definition:

Hemidesmosomes are small specialized structures that function to connect a cell to the extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars

Location:

  • Found on the basal side of the epithelial cell
  • Located between the cell and the extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars, connecting basal epithelial cells to the lamina lucida
  • Mainly found in keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions

Composition:

  • 2 classifications of hemidesmosomes:
    • Type 1 Type 1 Spinal Muscular Atrophy
      • Located in stratified and pseudostratified epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
      • Contain 5 main proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
    • Type 2 Type 2 Spinal Muscular Atrophy: contain fewer proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Multiprotein complex:
    • Integrin (transmembrane linker)
    • Keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis filaments
    • Basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN) ( laminin Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Connective Tissue: Histology, collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology)
  • Integrins Integrins A family of transmembrane glycoproteins (membrane glycoproteins) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix proteins; complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors(receptors, cytoadhesin), the leukocyte adhesion receptors (receptors, leukocyte adhesion), and the very late antigen receptors. Each family contains a common beta-subunit (integrin beta chains) combined with one or more distinct alpha-subunits (integrin alpha chains). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; hemostasis; thrombosis; wound healing; immune and nonimmune defense mechanisms; and oncogenic transformation. Leukocyte Adhesion Deficiency Type 1 integrate the intracellular cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton ( keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis) to the basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN).

Function:

  • Forms the dermal–epidermal junction Dermal–Epidermal Junction Bullous Pemphigoid and Pemphigus Vulgaris
  • Firm adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies of cells to basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN)

Disease:

Hemidesmosomes are important for keeping keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions attached to the basal lamina Basal Lamina Capillaries: Histology. Disease of these structures leads to blistering conditions ( epidermolysis bullosa Epidermolysis bullosa Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. Squamous Cell Carcinoma (SCC))

Types of cell junctions

Illustration of the 3 types of anchoring junctions that maintain cell shape

Image: “Types of Cell Junctions” by OpenStax College. License: CC BY 3.0, edited by Lecturio.

Gap Junctions

Definition

Gap junctions are protein channels Channels The Cell: Cell Membrane that connect the cytoplasm of 2 cells to allow for molecular passage. This structure may also be called a nexus or macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy communicans.

Gap cell junction

Gap junctions between 2 adjacent cells with multiple connexons

Image: “Gap cell junction” by Mariana Ruiz . License: Public Domain, edited by Lecturio.

Location

Composition

  • Connexons make up the gap junction.
    • Made of 6 connexin proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that span transmembranes
    • Form a tube with pores on either end
    • A pair of connexons connect within the intercellular space.
  • The intercellular space is between 2 and 4 nm.
  • Hemichannels consisting of the same proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are called homomeric.
  • Hemichannels consisting of different proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are called heteromeric.
Gap junction

Illustration of a gap junction

Image: “Types of Cell Junctions” by OpenStax College. License: CC BY 3.0, edited by Lecturio.

Function

  • Act as a way to communicate between cells
  • Form channels Channels The Cell: Cell Membrane that permit exchange of:
    • Ions (electrical impulses)
    • Regulatory molecules ( cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response)
    • Metabolites
  • Allow for coupling of the electrical and metabolic functions between cells
  • Mediate activation of 2nd messengers and their impacts on cellular function
  • Adhesive capability between neighboring cells

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Clinical Relevance

  • Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis: loss of E-cadherin E-cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer function results in weakening in the anchoring of cells via the adherens junction. The loss of E-cadherin E-cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer has been shown to increase cancer ( CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)) cell invasion. Cancer cells may migrate, causing metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis without the functionality of the adherens junction.
  • Pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris: a disease that is a type II hypersensitivity reaction Type II hypersensitivity reaction Type II hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by immunoglobulin G (IgG) and IgM antibodies directed against antigens on cells or extracellular materials. The reaction leads to cytotoxic processes involving antibodies and the complement system. Type II Hypersensitivity Reaction whereby autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques target the desmosome complex (desmogelin), which results in the loss of structural integrity, especially during shear forces on epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions, causing the dermal layer to slide off, forming bullae Bullae Erythema Multiforme. Despite being a rare condition, pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris is the most common form of pemphigus. The condition is progressive without treatment. The primary treatment is a corticosteroid.
  • Bullous pemphigoid Bullous pemphigoid Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. Bullous Pemphigoid and Pemphigus Vulgaris: a type II hypersensitivity reaction Type II hypersensitivity reaction Type II hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by immunoglobulin G (IgG) and IgM antibodies directed against antigens on cells or extracellular materials. The reaction leads to cytotoxic processes involving antibodies and the complement system. Type II Hypersensitivity Reaction whereby autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques target the hemidesmosome complex (desmogelin), which results in the loss of connection of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions to the dermal basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN). Diagnosis requires a classic clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and confirmatory findings on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with tense bullae Bullae Erythema Multiforme that rupture. Topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors are the main treatment modality.

References

  1. Alberts, B, Johnson, A, Lewis, J, et al. (2002). Cell junctions. Molecular Biology of the Cell, 4th Edition. New York: Garland Science. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26857/.
  2. (2016). Guyton and Hall textbook of medical physiology (13th edition.). Philadelphia, PA: Elsevier.
  3. Goodenough, DA, & Paul, DL. Gap junctions. (2009). Cold Spring Harb Perspect Biol. 2009;1(1):a002576. doi:10.1101/cshperspect.a002576
  4. Meng, W, & Takeichi, M. (2009). Adherens junction: Molecular architecture and regulation. Cold Spring Harb Perspect Biol. 2009;1(6):a002899. doi:10.1101/cshperspect.a002899
  5. Muse, ME, & Crane, JS. Physiology, epithelialization. [Updated 2021 Apr 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532977/.

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