Cell Communication and Cell Signaling Student Learning Guide

1. Introduction

There are many ways that, in response to the binding of a ligand with a receptor in the membrane, cells will change their internal activities. In what follows, we’re going to focus on only one: G-protein coupled receptors. That’s because that’s the kind of receptor found in the glycogen-storing liver cells that are tuned to respond to epinephrine by converting that glycogen into glucose (which is the story we’ve been trying to follow). Let’s see how.

2. G-Protein Coupled Receptors

A G-Protein coupled receptor is exactly what it sounds like. It’s a membrane receptor (“1,” at left) that works with a nearby membrane embedded protein called a G-protein (“2”). The name “G protein” relates to the interaction between these proteins and either GTP or GDP, two energy-transfer molecules that function very similarly to ATP and ADP. When a ligand (like epinephrine) binds with the receptor, the receptor activates the G-protein, which, in turn, activates a nearby membrane embedded enzyme (“4”), which sends a signal into the cytoplasm.

Using the diagrams below, we’ll see how this works. Note that the Roman numerals below represent a time sequence.

  • “I” (the same as what’s shown above) represents the moment before epinephrine binds.
  • “II” shows what happens at the moment of binding.
  • “III” shows both the changes that happen in response to epinephrine binding, and epinephrine’s detachment from the target cell membrane.
  • “IV” shows the deactivation of the cell’s initial response to epinephrine.

Read below, looking at the diagram to follow the action. Note that you can scroll the text below the diagram while continuing to be able to look at the diagram.

 

  1. Diagram “I” shows what the membrane (“b”), extracellular fluid (“a”), and cytoplasm (“c”) are like before epinephrine arrives at the cell. Embedded in the membrane is a receptor (“1”). This receptor is a transmembrane protein, spanning the entire membrane, and it’s associated with a nearby G protein (represented by “2”). At this moment, before epinephrine binds, the G protein is inactive, and bound to a molecule of GDP (at “”3”). GDP stands for guanosine diphosphate. You can think of GDP exactly as you would think of ADP, the low energy counterpart of ATP. Finally, there’s a membrane-embedded enzyme (at “4”). This enzyme is currently inactive; activating it is a key step in bringing about a cellular response.
  2. In diagram “II,” epinephrine (“8”) binds with the receptor (“1”). Epinephrine’s binding at the extracellular side of the receptor changes the receptor’s shape and binding properties on its cytoplasmic side. To understand this, remember what you’ve learned about allosteric regulation of enzymes (which you can review by clicking here). This change in the receptor enables it to bind with the G protein. This binding, in turn, changes the G protein so that it discharges its GDP, and binds instead with GTP (the high energy form of this molecular duo).
  3. In diagram “III,” two things happen.
    1. First the G protein, now bound to GTP, disconnects from the receptor and floats away within the membrane. Binding with GTP has changed the G protein’s shape so that it now can bind with the membrane-embedded enzyme (shown at “4”). When the G protein contacts this enzyme, the two bind in a way that causes a conformational change in this enzyme (again, another allosteric shift), triggering the start of the cellular response. This response is indicated by “5,” and we’ll focus on its mechanism in the next tutorial.
    2. Second, epinephrine disconnects from the receptor. Note that the bonds between ligand and receptor are always weak and short term, so nothing special needs to happen to get the ligand and receptor to disconnect.
  4. In step “IV,” GTP loses its terminal phosphate. You can see that phosphate group (at “10”) being released into the cytoplasm. This causes GTP to revert back to GDP, and the G protein reverts back to its inactive form. The G protein dissociates from the enzyme at “4,” which has the effect of deactivating the enzyme, which turns off this part of the cellular response.

The membrane is now ready to receive another signal, and whether or not that happens depends on whether the adrenal glands are releasing more epinephrine, which in turn depends on whether or not the initial stimulus for the fight or flight response is still present.

I’ve put together a quiz below to let you interact with the diagram and get your head around this material. But before doing that, let’s hone in on the membrane receptor itself. The receptor in this system is itself a tertiary-level protein. It consists of a ligand binding site (shown at “1”), a series of seven alpha-helices that thread through the phospholipid bilayer, and a G-protein binding site (“3”). As stated above, you  should think back to allosteric binding sites on enzymes to imagine the mechanism involved with a G-protein coupled receptor. When the ligand (epinephrine in this case) binds with the ligand-binding site, it causes a conformational change that ripples through the entire receptor protein. Most importantly, it changes the shape of “3” so that this cytoplasmic portion of the receptor can bind with the G protein, setting off the cascade of reactions that we described above.

Here’s the quiz.

3. Quiz: Reception

[qwiz random = “true” qrecord_id=”sciencemusicvideosMeister1961-Cell Signaling_Reception (M11)” style=”width: 750px !important;”]

[h] Quiz: Reception

[i]

[!!!]+++question 9++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|63a6fc0cb8fff” question_number=”1″] Which number represents the signal binding site?

[textentry single_char=”true”]

[c*] 1

[f] Yes. “1” is the signal binding site

[c] *

[f] No. Here’s a hint. The signal binding site is going to have to face the outside of the cell, and be something that a signal could bind with.
[!!!]+++question 10++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|63a174707b7ff” question_number=”2″] Which number represents the receptor segment that interacts with the G-Protein?

[textentry single_char=”true”]

[c*] 3

[f] Yes. “3” represents the segment of the receptor that interacts with a G-protein

[c] *

[f] No. The G-protein is embedded in the inner side of the plasma membrane. Which part of the receptor could interact with something that’s on the inside of the membrane?
[!!!]+++question 11++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|639bc7937fbff” question_number=”3″] The alpha helices that embed the receptor in the membrane are represented by which number (type in a 1, 2, or a 3)?

[textentry single_char=”true”]

[c*] 2

[f] Yes. “2” represents the alpha helices that embed this receptor in the cell membrane.

[c] *

[f] No. Here’s a hint: a helix is like a coiled spring.
[!!!]+++question 12++++++[/!!!!]

[q json=”true” multiple_choice=”true” dataset_id=”SMV_Reception (cell communication)|6394f0b091fff” question_number=”4″] Which roman numeral shows the phase in which a ligand is binding with a receptor?

 

[c] I

[f] No. “I” represents the phase before the ligand binds with the receptor.

[c*] II

[f] Excellent. “II” represents the phase where a ligand (a hormone such as epinephrine, for example) is binding with the receptor.

[c] III

[f] No. “III” shows the ligand dissociating from the receptor. Where do you see the ligand binding with the receptor?

[c] IV

[f] No. “IV” shows the G protein reverting to its inactive form as it converts its GTP to GDP. Where do you see the ligand binding with the receptor?
[!!!]+++question 13++++++[/!!!!]

[q json=”true” multiple_choice=”true” dataset_id=”SMV_Reception (cell communication)|638e898fdefff” question_number=”5″] Which roman numeral shows the phase in which the G protein is becoming activated as it replaces its GDP with a GTP?

[c] I

[f] No. “I” represents the phase where the G protein is bound to GDP (meaning that the G protein is in an inactive form).

[c*] II

[f] Excellent. “II” represents the phase where a ligand (a hormone such as epinephrine, for example) is binding with the receptor. This changes a segment on the receptor, which in turn modifies the G protein, causing it to replace GDP with GTP.

[c] III

[f] No. “III” shows the ligand dissociating from the receptor, and an activated G protein binding with a membrane bound enzyme. Which phase shows the activation of the G protein?

[c] IV

[f] No. “IV” shows the G protein reverting to its inactive form as it converts its GTP to GDP.Which phase shows the activation of the G protein?
[!!!]+++question 14++++++[/!!!!]

 

[q json=”true” multiple_choice=”true” dataset_id=”SMV_Reception (cell communication)|6385a92289bff” question_number=”6″] Which roman numeral shows the phase in which an activated G protein is activating a membrane-bound enzyme?

[c] I

[f] No. “I” represents the phase where the G protein is bound to GDP (meaning that the G protein is in an inactive form). Where do you see an activated G protein interacting with a membrane bound enzyme?

[c] II

[f] No. “II” represents the phase where a ligand (a hormone such as epinephrine, for example) is binding with the receptor. This changes a segment on the receptor, which in turn modifies the G protein, causing it to replace GDP with GTP. But there’s no interaction between the G protein and the membrane bound enzyme (at “4”).

[c*] III

[f] Yes. “III” shows the ligand dissociating from the receptor, and an activated G protein binding with a membrane bound enzyme.

[c] IV

[f] No. “IV” shows the G protein reverting to its inactive form as it converts its GTP to GDP. Where do you see an activated G protein interacting with a membrane bound enzyme?
[!!!]+++question 15++++++[/!!!!]

 

[q json=”true” multiple_choice=”true” dataset_id=”SMV_Reception (cell communication)|637fb1c4117ff” question_number=”7″] Which roman numeral shows the phase in which a G protein is reverting back to its inactive form, and in which cellular responses stop occurring.

[c] I

[f] No. “I” represents the phase where the G protein is bound to GDP (meaning that the G protein is in an inactive form). This question is asking you how the G protein became deactivated, with an attached GTP becoming converted to GDP.

[c] II

[f] No. “II” represents the phase where a ligand (a hormone such as epinephrine, for example) is binding with the receptor. This changes a segment on the receptor, which in turn modifies the G protein, causing it to replace GDP with GTP. This question is asking you how the G protein becomes deactivated, with its attached GTP being converted to GDP.

[c] III

[f] No. “III” shows the ligand dissociating from the receptor, and an activated G protein binding with a membrane bound enzyme. This question is asking you how the G protein becomes deactivated, with its attached GTP being converted to GDP.

[c*] IV

[f] Yes. “IV” shows the G protein reverting to its inactive form as it converts its GTP to GDP.
[!!!]+++question 16++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|6379dfa6577ff” question_number=”8″] In the series of diagrams below, which letter represents the cell membrane?

[textentry single_char=”true”]

[c*] b

[f] Yes. Letter“b” represents the cell membrane

[c] *

[f] No. Here’s a hint. If “c” is the cytoplasm, what letter has to be the membrane?
[!!!]+++question 17++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|63740d889d7ff” question_number=”9″] In the series of diagrams below, which number represents the receptor?

[textentry single_char=”true”]

[c*] 1

[f] Yes. “1” represents the receptor.

[c] *

[f] No. Here’s a hint. If “8” represents the ligand (the molecule that binds with the receptor), then which number has to represent the receptor itself?
[!!!]+++question 18++++++[/!!!!]

 

[q json=”true” dataset_id=”SMV_Reception (cell communication)|636e3b6ae37ff” question_number=”10″] In the series of diagrams below, which number represents the G protein?

[textentry single_char=”true”]

[c*] 2

[f] Yes. “2” represents the G protein.

[c] *

[f] No. Here’s a hint. The G protein is activated by the receptor, and then goes on to activate a membrane bound enzyme (such as the one depicted in number “4”). Of all of the components of this system, which one could possible play such a role?
[!!!]+++question 19++++++[/!!!!]

 

[q json=”true” dataset_id=”SMV_Reception (cell communication)|6367f98aeebff” question_number=”11″] In the series of diagrams below, which number represents GDP?

[textentry single_char=”true”]

[c*] 3

[f] Yes. “3” represents GDP (guanosine triphosphate). GDP is analogous to ADP (adenosine diphosphate) in that it can be phosphorylated to become a higher energy, activated form: GTP or guanosine triphosphate. That’s exactly what happens in this system: As GDP become GTP, the G protein become activated, enabling it to interact with a membrane bound enzyme to bring about a cellular response to the binding of the ligand.

[c] *

[f] No. Here’s a hint. GDP ((guanosine diphosphate) is a low energy form of GTP (triphosphate). When GDP is bound to a G protein, that protein is essentially inert. What do you see that’s bound to the G protein that can be transformed from a low energy state into a high energy state?
[!!!]+++question 20++++++[/!!!!]

 

[q json=”true” dataset_id=”SMV_Reception (cell communication)|636271eeb13ff” question_number=”12″] In the series of diagrams below, which number represents a membrane bound enzyme which, when activated, can initiate a cellular response?

[textentry single_char=”true”]

[c*] 4

[f] Yes. “4” represents a membrane bound enzyme. When this enzyme becomes activated, it can, in turn, activate other molecules which can bring about a cellular response.

[c] *

[f] No. Here’s a hint. Look for something that’s bound to the membrane that’s not a receptor or a G protein.
[!!!]+++question 21++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|635c9fd0f73ff” question_number=”13″] In the series of diagrams below, which number represents GTP?

[textentry single_char=”true”]

[c*] 9

[f] Yes. “9” represents GTP. When GTP binds to the G protein, the G protein becomes activated, allowing it to interact with membrane bound enzymes that can, in turn, initiate the cellular response.

[c] *

[f] No. Here’s a hint. GTP is an activated form of GDP. In this system, both can be found bound to the G protein. So, look for something that’s bound to a G protein, and which is represented as being in a high energy state.
[!!!]+++question 22++++++[/!!!!]

[q json=”true” dataset_id=”SMV_Reception (cell communication)|63565df1027ff” question_number=”14″] In the series of diagrams below, which number represents the cytoplasmic response to the binding of a ligand?

[textentry single_char=”true”]

[c*] 5

[f] Yes. “5” represents the cytoplasmic response to the binding of a ligand.

[c] *

[f] No. The cytoplasmic response comes about as a result of activities by membrane-bound enzymes that have been activated by the G protein (which was activated by the receptor, which was activated by the ligand). Study the diagram, and find the cytoplasmic response that’s at the end of this chain.
[!!!]+++question 23++++++[/!!!!]

[q json=”true” multiple_choice=”true” dataset_id=”SMV_Reception (cell communication)|634fd18f913ff” question_number=”15″] The G protein can be deactivated, bringing the cellular response to a close, when the GTP that’s bound to the G protein is converted to GDP. In the series of diagrams below, which number represents the phosphate group that is released during this conversion?

[c] 2

[f] No. “2” represents the G protein.

[c] 3

[f] No. “3” represents the GDP.

[c] 9

[f] No. “9” represents the GTP.

[c*] 10

[f] Way to go. “10” represents the phosphate that’s removed from GTP. Loss of this phosphate converts GTP to GDP, which renders the G protein into an inactive form.

[q json=”true” dataset_id=”SMV_Reception (cell communication)|634a49f353bff” question_number=”16″] In the diagram below, number 3 is [hangman]

[c] GDP

[f] Good!

[q json=”true” dataset_id=”SMV_Reception (cell communication)|6344e797d47ff” question_number=”17″] In the diagram below, number 9 is [hangman]

[c] GTP

[f] Good!

[q json=”true” dataset_id=”SMV_Reception (cell communication)|633f157a1a7ff” question_number=”18″] In the diagram below, number 4 is a membrane embedded [hangman]

[c] enzyme

[f] Good!

[q json=”true” dataset_id=”SMV_Reception (cell communication)|6339689d1ebff” question_number=”19″] If the diagram below were about mobilization of glucose from glycogen storing liver cells, then number 8 would be the hormone [hangman]

[c] epinephrine

[f] Good!

[q json=”true” dataset_id=”SMV_Reception (cell communication)|6333bbc022fff” question_number=”20″] In the diagram below, number 10 is a _________ group [hangman].

[c] phosphate

[f] Good!

[q json=”true” dataset_id=”SMV_Reception (cell communication)|632dc461aabff” question_number=”21″] In the diagram below, number 1 is a G-coupled protein [hangman].

[c] receptor

[f] Good!

[x]

[restart]

[/qwiz]

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