Receptors and Messengers

by Kevin Ahern, PhD

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    00:01 This picture depicts a hormone receptor in orange and a hormone in yellow that binds to it.

    00:07 Now as I said earlier, most hormone receptors are membrane bound, embedded in the membrane.

    00:12 And most steroid hormone receptors are found in the cytoplasm or nucleus.

    00:17 It’s the interaction of the hormone with the receptor that causes the signal which the hormone is communicating ultimately to be exerted inside of the cell.

    00:26 Now this simple figure schematically shows what’s happening.

    00:30 We can see on the left that the hormone is getting ready to bind to the receptor.

    00:35 And on the right we can see the hormone after it is bound to the receptor.

    00:39 On the outside part of the cell, which is the top layer here, that’s where the hormone is found, we see that there's a binding site for that hormone.

    00:47 And on the bottom side of the receptor which is the inside of the cell, we see that after the hormone binds, that part of the protein changes shape very slightly.

    00:58 Now very slight change in shape of that protein changes the interaction of that protein with molecules that are on the inside of the cell.

    01:07 So what we’re seeing here is the first step of communication, and we’re seeing how that communication actually ultimately will exert its effects.

    01:16 So this picture depicts two different ways in which signals can be communicated inside the cell.

    01:23 On the left we see steroid hormones, and as I said, steroid hormones are unusual in being able to navigate that lipid bilayer all by themselves.

    01:32 They get inside of the cytoplasm which is that middle layer that’s there.

    01:36 And you see that they bind to that purple colored molecule.

    01:39 That purple colored molecule is a steroid receptor floating around in the cytoplasm.

    01:46 When that steroid receptor binds to the hormone, you can see that it navigates downwards, and downwards it’s moving towards the nucleus, because the steroid hormone receptors are going to go and directly bind to DNA and stimulate the expression of specific genes that cause that hormone’s actions to ultimately be realized.

    02:06 The other figure that’s shown on the screen is showing what’s happening with a receptor that is not a steroid hormone receptor.

    02:13 Here we see that this is a membrane-bound receptor.

    02:17 And to orient you, the outside part of the cell is upwards, and like before, moving downwards, we’re moving closer to the nucleus.

    02:24 You can see the hormone that is floating in solution and you can see one hormone that has bound to its receptor.

    02:30 We can also see below that, a series of different boxes and circles, and colors and so forth; each one of those molecules being an individual protein.

    02:41 Now the binding of the membrane to the receptor caused a complex to form.

    02:47 And that complex is involved in communicating a signal downwards.

    02:52 So when we look at this membrane-bound receptor, we see that the complexity of the signal moving through the cell can be quite enormous.

    03:00 If we think about for example, how our computers connect to the internet, we think it has to go through for example, WiFi, and that WiFi has to be connected to another system, and that to another system, etcetera.

    03:10 Each of those being a node in that overall connection of your computer to a bigger computer elsewhere.

    03:16 Well that’s very much like what’s happening here, but surprisingly there’s quite a few proteins involved in the process, and we’ll see how that occurs.

    03:25 So after that initial receptor has bound to the hormone, that signal has to be communicated inwards.

    03:32 And as you saw in the example I showed for one protein, that was a membrane receptor, there were other proteins along the way that communicated signals.

    03:40 I also want to remind you that not all of the molecules involved in communicating messages are proteins on the inside of the cell.

    03:48 Some of the communicators as it were, are called second messengers.

    03:52 And what these messengers are, are small molecules that do the work of communicating that information.

    03:58 We can see some of them here.

    04:01 First we see one called IP3.

    04:03 It’s relatively small.

    04:04 When I say small, I’m meaning smaller than a protein.

    04:08 Another very common one found inside of cells is cyclic AMP.

    04:12 It’s related to the molecule AMP and the molecule ATP, but has a cyclic group as you can see on the left side of the molecule.

    04:21 Calcium as I’ve talked about in other lectures, performs functions of second messengers as well and happens as a result of release into the cytoplasm of the cell.

    04:31 Another cyclic nucleotide that’s involved in communicating information as a second messenger is cyclic GMP.

    04:37 And we’ve talked in another lecture about how cyclic GMP helps communicate information in the process of vision.

    04:46 Now, the covalent modification occurs during the communication of the message.

    04:51 So I showed in that previous slide, a variety of proteins, that one going to another, to another, to another, to another, down ultimately to the nucleus.

    05:00 What’s happening there? Well what’s happening is, each of those proteins is being modified chemically as that information is being communicated.

    05:09 That chemical modification is usually a phosphate that’s either put onto or taken off a protein.

    05:16 And that chemical modification is essentially the signal.

    05:20 So the signal you’re probably beginning to realize is complex.

    05:24 It can be coming in the form of second messengers, the small molecules you see here.

    05:28 It can be coming in the form of chemical modifications that are happening to proteins as well.

    05:34 Now, one of the things that happens ultimately in the communication of many messages, is alteration of the pattern of gene expression for a given cell.

    05:44 Remember that a cell in a multicellular organism has different genes that it expresses at different times.

    05:50 A bone cell for example, having different genes expressed than a muscle cell.

    05:55 So being able to control which genes are being expressed, allows that cell to respond appropriately to the needs of the body and the individual needs of that cell.

    06:06 Another way in which hormones can communicate and change the path of the cell is by changing the activity of enzymes within it, and we’ll see an example in just a little bit about how the process of glycogen metabolism can be drastically changed by action of a hormone.

    06:26 So this figure depicts a simple scheme of second messengers involved with a protein called phospholipase C.

    06:34 So phospholipase C is an enzyme that’s found in the membrane of cells and it gets activated by hormone action.

    06:41 Now this is a very fast acting process because what’s happening in this process is we’re seeing an enzyme being activated, phospholipase C.

    06:49 When it’s activated, phospholipase C catalyses a reaction on a molecule called PIP2 in the cell’s lipid bilayer.

    06:58 That reaction catalyzed by phospholipase C splits PIP2 into two molecules.

    07:05 One of the molecules is known as IP3, and you can see it traversing the cytoplasm of the cell, moving downwards in the direction of the endoplasmic reticulum, an organelle that holds calcium for example.

    07:18 When IP3 gets to a receptor on the surface of the endoplasmic reticulum, it binds to it and causes calcium to be released into the cytoplasm of the cell.

    07:30 Calcium is also a second messenger.

    07:32 So we’ve seen, now it’s two second messengers, one being IP3 and a second one being the calcium that’s released from the endoplasmic reticulum.

    07:40 The calcium goes and binds to a protein known as protein kinase C.

    07:46 Now protein kinase C is a protein that can physically alter other proteins.

    07:52 Remember I said we can covalently modify other proteins.

    07:55 So that’s what is happening as calcium binds to protein kinase C.

    08:00 Well turns out for protein kinase C to be fully active, it needs an additional second messenger that is a third second messenger.

    08:08 And the third second messenger that it uses is embedded in the lipid bilayer of the cell and is known as DAG.

    08:16 Now not coincidentally, DAG was the product of the catalysis of phospholipase C on PIP2.

    08:24 So when phospholipase C cleaves PIP2, it broke it into IP3 and DAG.

    08:30 Both of those went to different places to exert their effects.

    08:34 But the coordinated effort was to activate the protein known as protein kinase C.

    08:40 Protein kinase C can go phosphorylate other proteins and cause the cell to change its gene expression.

    08:48 Now, this pattern of modifying proteins can be very complex.

    08:52 It’s amazing the network of individual processes that are occurring inside of cells.

    08:57 So don’t worry, I’m not going to take you through all of this.

    09:00 Suffice it to say there’s an entire course we could probably teach on what’s shown on this one slide here.

    09:05 But the message I want you to take away is that in this process that you’re seeing, there are multiple components that are all interacting and coordinating an effort that is focused in this case, in the nucleus.

    09:18 And the nucleus of course is where the DNA is held, and it’s there where the gene expression will be controlled as a result of the processes that are happening through these hormone signaling processes.

    09:28 So, cellular signaling is very complex.

    09:32 And the responses in every case though are aimed at benefiting the organism, just like that military where I have an individual soldier.

    09:41 The soldier’s effort is to help the unit as a whole.

    09:45 So too are the actions of cells directed to helping the organism as a whole.

    About the Lecture

    The lecture Receptors and Messengers by Kevin Ahern, PhD is from the course Hormones and Signal Transduction. It contains the following chapters:

    • Receptors
    • Receipt of Message
    • Second Messengers

    Included Quiz Questions

    1. They change shape when binding occurs.
    2. They are always membrane bound.
    3. They change shape on binding to another receptor.
    4. They require co-factors to be stimulated.
    5. They are specific to a single type of substance.
    1. They use covalent interactions to modify proteins.
    2. They use hydrogen interactions to modify proteins.
    3. They carry messages out of cells.
    4. They use van der Waals forces to modify proteins.
    1. Inositol-1, 4, 5-triphosphate
    2. Deoxyribose nucleic acid
    3. cAMP
    4. cGMP
    5. Ca+2 ions
    1. Covalent changes in protein molecules.
    2. Hydration of protein molecules.
    3. Dehydration of protein molecules.
    4. Conversion of triple bonds to double bonds between the 2 carbon atoms of a protein molecule.
    5. Conversion of triple bonds to single bonds between the 2 carbon atoms of a protein molecule.
    1. An activated phospholipase C enzyme catalyzes the breakdown of the PIP2 molecule to IP3 and DAG.
    2. Phospholipase C protein acts as a second messenger that directly stimulates the gene expressions by binding with the DNA molecules.
    3. Phospholipase C protein acts as a second messenger molecule for the synthesis of PIP2 from DAG and IP3.
    4. Phospholipase C acts as an energy source for the transduction of extracellular response toward the Golgi apparatus.

    Author of lecture Receptors and Messengers

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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    Very good!
    By Laura P. on 11. May 2017 for Receptors and Messengers

    Thank you Dr. Kevin Ahern!!! Sometimes you speak so fast, but these time was perfect :)