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Communication and Signaling – Protein Movement and Cell Signaling

by Kevin Ahern, PhD
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    00:00 you can see at the very bottom.

    00:01 Another important function performed by proteins is that of signaling. Now signaling is also known as communication and I’d like to think about it as the way that the cell responds to its environment, especially in a multicellular organism this is very important. It's important for all of the different tissues of the organs to be pulling the oars at the same time and not countering each other. The liver has specialized functions for example, to control the amount of glucose and fat and so forth that's released into the bloodstream. So it's important that the liver be able to respond to and hear signals that other cells in the body telling it about the need for various nutrients, so this signaling is very, very important.

    00:46 Now there are several different levels of signaling and several different proteins that are involved in the signaling process. In fact there are many proteins involved, because there are many different signaling processes, but I’m going to talk about them here in very general terms. So the first level I want to talk about are the membrane receptor proteins.

    01:04 Now these play an absolutely critical function because it's through these proteins that the signal must be transmitted from outside of the cell to inside of the cell. Now that is absolutely essential, if my liver cell and the rest of the body is telling me I need glucose, that information has to get inside the cell, where the glucose can be made and released, for the body to have the glucose that it needs, so that transmission of information happens through a membrane receptor. The membrane receptor proteins are what we call integral proteins, that is they are embedded in the lipid bilayer as you can see in the figure on the right. They are surrounded by the lipid bilayer in fact, with a part of them projecting above it, in this case meaning outside of the cell, and part of it projecting below it, in this case inside of the cell.

    01:57 The membrane proteins themselves are known as 7TMs and the TM stands for transmembrane.

    02:05 So as we look at this illustrative figure on the right, this protein has seven different coil domains and they are actually numbered on there but they are a little hard to see.

    02:14 The seven different coil domains that are going back and forth across the lipid bilayer and that going back and forth with these different domains occur seven times. Many of the proteins are 7TMs, and 7TMs is actually a common category of membrane proteins.

    02:31 The membrane receptors bind to what's called a messenger molecule. So that messenger molecule is being sent by other cells in the body. The messenger molecule binds to the receptor protein on the outside of the cell, and that binding to the receptor causes the receptor to change shape on the inside of the cell. Then that change on the inside of the cell causes everything else to happen. The things that happen on the inside of the cell usually results in the formation of what's called a second messenger, and we’ll see that in just a little bit.

    03:04 Another important function in the signaling process is that of peptide hormones. Now I've already described the first messengers that are released by cells to go to the target cell to bind.

    03:16 Those hormones are oftentimes proteins themselves. These are released and made by the endocrine system. And some examples of these peptide hormones include insulin, which is very commonly known, oxytocin, and glucagon among many others. Inside the cell, there are proteins that play very important roles in communicating that information that has come in from the outside.

    03:41 Now these proteins can have a variety of different functions, but one of the very common functions that many of them have is that they are kinases. What kinases do is they put phosphates onto other proteins. So it’s actually a cascade of kinases that can happen, one protein phosphorylating another protein, which causes that protein to become active and phosphorylate another protein, and a signal is communicated from one protein to another as result of this kinase action. That’s only one example, there are many others.

    04:14 The last important function I want to talk about that proteins play in the signaling process is that of functioning as transcription factors. Transcription of course is the process whereby information in DNA, is transferred into messenger RNA in the process of transcription.

    04:28 The ability of RNA polymerase to start the synthesis of RNA is a function of proteins that tell it where to start synthesis. Transcription factors play a role in this process, they can either turn on transcriptions of specific genes or turn off transcription of specific genes, depending upon the actual function. As a result of all the signaling events and signaling proteins that happen, a cell can then respond to the outside signal in the way that the body needs it to respond. Whether it is releasing nutrients, whether it's telling it to divide, or whether it's telling it to do other things that might be beneficial.

    05:04 This slide actually illustrates the signaling process for a liver cell. Now it doesn't show the transcription that I talked about before, but it shows many of the other steps in the process. In this slide we can see at the top left, a protein that's embedded in the membrane that’s actually the signaling protein. It is called the beta-adrenergic receptor. And as you can see it's a 7TM, that is, it has seven domains crossing the lipid bilayer.

    05:29 On the right bottom of the beta-adrenergic receptor, we can see an interesting protein that has three units, an alpha unit, a beta unit and a gamma unit. And that alpha, beta, gamma is part of what we call a G-protein. That G-protein has an important function and it’s carrying a nucleotide called GDP. In this state it's not active, it's not stimulating any process, but when the adrenergic receptor binds to the hormone from outside of the liver cell, the receptor changes its shape and that change in shape causes a change in the G-protein.

    06:05 The change in the G-protein causes a couple of things to happen. First of all, the G-protein releases the beta and the gamma as it binds a GTP in place of the GDP. When this happens, the G-protein then moves over to an enzyme that is also embedded in the membrane called adenylate cyclase. What adenylate cyclase does when it’s stimulated by this G-protein, is it causes the formation of a molecule called cyclic AMP, that's converted from ATP as you can see here. Now cyclic AMP is a molecule that we call the second messenger. The first messenger was the hormone outside of the cell that caused the receptor to be activated. The cyclic AMP on the other hand is an internal molecule that is going to activate an enzyme. The enzyme that gets activated by cyclic AMP is protein kinase A, and protein kinase A is one of those kinases I talked about. It phosphorylates another enzyme called phosphorylase kinase and in the process causes that enzyme to become activated, where it previously was inactivated. The phosphorylase kinase in turn, phosphorylates another enzyme called glycogen phosphorylase B, converting it into glycogen phosphorylase A. At that point the glycogen phosphorylase A is active, and that glycogen phosphorylase A then breaks down glycogen to produce molecules of glucose.


    About the Lecture

    The lecture Communication and Signaling – Protein Movement and Cell Signaling by Kevin Ahern, PhD is from the course Biochemistry: Basics.


    Included Quiz Questions

    1. It involves hormones
    2. Signaling molecules enter cells through protein receptors
    3. The term 7TM refers to a second messenger
    4. The entire process occurs in the lipid bilayer
    1. Testosterone
    2. Oxytocin
    3. Glucagon
    4. Calcitonin
    5. Insulin
    1. Fibrous proteins
    2. Peptide hormones
    3. Cell membrane receptors
    4. Kinase enzymes
    5. Transcription factors
    1. Integral membrane proteins with seven membrane-spanning helices and they participate in signal transduction
    2. Peripheral membrane proteins present on the outside of the cell membrane and transduce the signal to the interior of the cell
    3. Peripheral membrane proteins present on the inside of the cell membrane and transduce the signal to the exterior of the cell
    4. Highly hydrophilic membrane proteins present on the outside of the cell membrane and provide the structural strength to the cell membrane
    5. Highly hydrophobic membrane proteins present in the cell membrane and provide the shape to cell structures

    Author of lecture Communication and Signaling – Protein Movement and Cell Signaling

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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    Your explanation is making sense and connect biochemistry with real life!
    By mei huah c. on 16. May 2018 for Communication and Signaling – Protein Movement and Cell Signaling

    I like the way you link things from one to another. Yuu made these lectures highly appreciated with the concise and comprehensive explanation! Thanks Prof!