Chapter 11: Cell Communication Chapters 9, 10, and 11 form three of the most difficult chapters in the book. The special challenge in Chapter 11 is not that the material is so difficult, but that most of the material will be completely new to you. Cell communication is normally not covered in standard high school biology books, yet perhaps no other section of biology has grown as much as cell signaling has in the last ten years. Take your time with this section, and you will be rewarded with a knowledge base that will be most helpful in this course and courses to come.

Concept 11.1 External signals are converted into responses within the cell 1. What is a signal transduction pathway? •A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response •Signal transduction pathways convert signals on a cell’s surface into cellular responses 2.

How does yeast mating serve as an example of a signal

transduction pathway? Figure 11.2 illustrates the communication between mating yeast cells including the (1) Exchanges of mating factors, (2) The mating, and (3) the new a/ cell.

3. Complete the chart of local chemical signaling in cell communication in animals. •In many cases, animal cells communicate using local regulators, messenger molecules that travel only short distances

Local Signaling Types Paracrine Synaptic

Specific Secretes through local regulator, diffusing via secretory vesicles and is released into the target cell. Electrical signal along nerve triggers the ending (cleft) to secrete neurotransmitter where it diffuses across synapse. The targeted cell is stimulated

4. How does a hormone qualify as a long-distance signaling example? The hormone must travel through the bloodstream to reach its target celled area.

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A signal transduction pathway has three stages. Use Figure 11.6 to label the missing parts of the preview figure below, and then explain each step. 1. Reception: A signal molecule binds to a receptor protein, causing it to change shape; 2. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell; and 3. Response: Cell signaling leads to regulation of transcription or cytoplasmic activities

Concept 11.2 Reception: A signal molecule binds to a receptor protein, causing it to change shape Explain the term ligand. (This term is not restricted to cell signaling. You will see it in other situations during the year.) •It is the binding between a signal molecule (ligand) and receptor. It is highly specific. •A shape change in a receptor is often the initial transduction of the signal •Most signal receptors are plasma membrane proteins 6.

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The text will explain three major types of membrane receptors in Figure 11.7. This material is of fundamental importance, so we will work thorough the specific figures for each type of membrane receptor. The first example is a G protein-linked receptor. In the first figure, label the components and then describe the role of the three components. •There are three main types of membrane receptors: –G protein-coupled receptors

1. (1) G protein-coupled receptor is a plasma membrane receptor loosely attached to the cytoplasm side of the membrane, the G-protein is a molecular switch that is either on or off, depending on which of two guanine nucleotides is attached, GDP or GTP. Hence, the term G-protein. GTP is similar to ATP. When (2) GDP is bound to the G-protein, as shown in the figure below, the G-protein is inactive. The receptor and G-protein work together with another protein, which is usually an (3) enzyme; –Receptor tyrosine kinases: •Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines •A receptor tyrosine kinase can trigger multiple signal transduction pathways at once –Ion channel receptors

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Label and then describe what happens in step 2. 2. When the appropriate signaling molecule binds to the extracellular side of the receptor, the receptor is activated and changes shape. Its cytoplasmic side then binds to an inactive G-protein causing a GTP to displace the GDP. This activates the G-protein.

9. Label, then describe what happens in step 3. (The yellow box at the bottom right is important!). 3. The activated G-protein dissociates from the receptor, diffuses along the membrane, and then binds to an enzyme, altering the enzymes shape and activity. When the enzyme is activated, it can trigger the next step in a pathway leading to a cellular response. 10.

Equally important to starting a signal is stopping a signal. Step 4 stops the

signal. (Failure to do so can lead to serious problems, like cancer.) Label and then describe how the signal is halted. 4. The changes in the enzyme and G protein are only temporary because the Gprotein, also, functions as a GTPase enzyme – in other words – it hydrolyzes its bound GTP to GDP. Now inactive again, the G-protein leaves the enzyme, which returns to its original state. The G-protein is now available for reuse. The GTPase function of the G-protein allows the pathway to shut down rapidly, when the signaling molecule is no longer present. 11. What activates a G protein? •A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein •The G protein acts as an on/off switch: If GDP is bound to the G-protein, the Gprotein is inactive. 12. A G protein is also a GTPase enzyme. Why is this important? •The changes in the enzyme and G protein are only temporary because the G-protein, also, functions as a GTPase enzyme – in other words – it hydrolyzes its bound GTP to GDP. 13.

The second type of receptor described is receptor tyrosine kinase. Explain what a kinase enzyme does. Attaches phosphates to trigger.

14. How does tyrosine kinase function in the membrane receptor? •Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines 15.

What is a key difference between receptor tyrosine kinases •A receptor

tyrosine kinase can trigger multiple signal transduction pathways at once; and G protein-coupled receptors, while the G-protein is a molecular switch that is either on or off, depending on which of two guanine nucleotides is attached, GDP or GTP. ? 16. Provide all of the missing labels on the diagram; then explain what happens in step 1. 1. Many receptor tyrosine kinases have the structure depicted schematically here. Before the signaling molecule binds, the receptors exist as individual polypeptides. Notice that each has an extra-cellular ligand-binding site, an alpha helix spanning the membrane, and an intra-cellular tail containing multiple tyrosines.

17. Label step 2 and then describe what happens to receptors tyrosine kinases when signaling molecules have attached. 2. The binding of a signal molecule (such a s a growth factor) causes two receptor polypeptides to associate closely with each other for a dime (dimerization). 18. Label and explain how the receptors are activated in step 3. 3. Dimerization activates the tyrosine kinase region of each polypeptide, each tyrosine kinase adds a phosphate from an ATP molecule to a tyrosine on the tail of the other polypeptide. 19.

Use step 4 to explain how the activated receptor can stimulate multiple cellular response pathways.

4. Now that the receptor protein is fully activated, recognized by specific relay proteins inside the cell. Each such protein binds to a specific phosphorylated tyrosine, undergoing a resulting structural change that activates the bound protein. Each activated protein triggers a transduction pathway, leading to a cellular response. 20.

Each activated protein in the figure above triggers a signal transduction pathway leading to a cellular response. •A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

Moving to ion channel receptors, the example in Figure 11.7 shows the flow of ions into the cell. Ion channel receptors can also stop the flow of ions. These comparatively simple membrane receptors are explained in three steps. In the first step, label the diagram and then explain the role of the labeled molecules. 1. In (1) a ligand-gated ion channel receptor is illustrated in which the gate remains closed until a ligand binds to the receptor.

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Label the diagram and then explain what has happened with the binding of the ligand to the receptor. When the ligand binds to the receptor as is illustrated in (2) below, and the gate opens; specific ions can flow through the channel and rapidly change the concentration of that particular ion inside the cell. This change may directly affect the activity of the cell in some way.

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The ligand attachment to the receptor is brief. Label and explain what

happens as the ligand dissociates. When the ligand dissociates from the receptor, as illustrated in (3) below, the gate closes; and ions no longer enter the cell. 24.

In what body system are ligand-gated ion channels and voltage-gated ion channels of particular importance? Nervous system

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Intracellular receptors are found in the cytosol or nucleus of the cell, where they bond to chemical messengers that are hydrophobic or very small, like nitric oxide.

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This diagram uses testosterone, a hydrophobic hormone, to detail how intracellular receptors work. At each arrow, add an explanation of what is happening in the cell.

An important idea, transcription factors, is introduced in Figure 11.8. Explain the function of transcription factors in the cell. •An activated hormone-receptor complex can act as a transcription factor, turning on specific genes. By acting as a transcription factor, the testosterone receptor itself carries out the complete transduction of the signal. 27.

Concept 11.3 Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell 28. What are two benefits of multistep pathways like the one in Figure 11.9? •In many pathways, the signal is transmitted by a cascade of protein phosphorylations, and •protein kinases are able to transfer phosphates from ATP to protein. This process is called phosphorylation. •Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation •This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off 29. Explain the role of these two categories of enzymes in transduction. 1. Protein kinase: Protein kinases (noted above) are able to transfer phosphates from ATP to protein. This is called phosphorylation. 2. Protein phosphatases: •Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation •This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off. 30. Using Figure 11.9 as your guide, explain what is occurring in the cell at each arrow.

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What is the difference between a first messenger and a second messenger?

•The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” •Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion •Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases •Cyclic AMP and calcium ions are common second messengers •Cyclic AMP (cAMP) is one of the most widely used second messengers 32.

Two common second messengers are cyclic AMP (cAMP) and calcium ions (Ca2+). Explain the role of the second messenger cAMP in Figure 11.11 from the text. Cyclic AMP (cAMP) a s a second messenger in a G-protein signaling pathway: The first messenger activates a G-prtotein in turn, the G-protein activates adenylyl cyclase, an enzyme in the plasma membrane, which catalyzes (converts) ATP to cAMP. The cAMP then acts as a second messenger activating another protein, usually protein kinase A, leading to cellular responses.

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What is the important relationship between the second messenger and protein kinase A? As stated above, cAMP acts as a second messenger activating another protein, usually protein kinase A. This leads to cellular responses.

34. Figure 11.11 explains how to initiate a cellular response; how might that response be inhibited? Phosphorylation and de-phosphorylation system acts as a molecular switch, turning activities on and off. •Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase. 35. Using your new knowledge of cell signaling, explain the mechanism of disease in cholera. Cholera is characterized by severe water loss, vomiting and muscle cramps. It is caused by infection with the Gram-negative bacterium Vibrio cholerae, which secretes cholera toxin (CT) that can activate the cyclic AMP signalling pathway. CT is composed of a catalytic A subunit and five B subunits. The latter attach the toxin to the surface of the cell, where they function as membrane-penetration subunits that inject the catalytic subunit into the cell. The toxin interacts with a G M1 ganglioside on the cell surface of intestinal epithelial cells, and this enables the A subunit to enter the cell, where it stimulates fluid secretion by activating cyclic AMP formation. The catalytic A subunit catalyses the transfer of ADP-ribose from NAD to an arginine group on the α subunit of GS. This ADP ribosylation inhibits the ability of GS to hydrolyse GTP, which means that this G protein is locked in its active configuration and thus maintains a persistent activation of cyclic AMP and intestinal secretion. 36. List three types of pathways often induced by calcium ions. 1. •A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol; 2. •Pathways leading to the release of calcium involve inositol triphosphate (IP3); and 3. •Diacylglycerol (DAG) as additional second messengers. 37.

What happens to the cytoplasmic concentration of calcium when it is used as a second messenger? •Calcium ions (Ca2+) act as a second messenger in many pathways; and •Calcium is an important second messenger because cells can regulate its concentration.

Concept 11.4 Response: Cell signaling leads to regulation of transcription or cytoplasmic activities 38. When cell signaling causes a response in the nucleus, what normally happens?

•The cell’s response to an extracellular signal is sometimes called the “output response” •Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities •Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities •The response may occur in the cytoplasm or may involve action in the nucleus •Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus •The final activated molecule may function as a transcription factor as a response 39. When cell signaling causes a response in the cytoplasm, what normally happens? Phosphorylation cascade, in Figure 11.15 see below Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine.

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Figure 11.15 shows a single molecule of epinephrine resulting in the

formation of the stimulation of glycogen breakdown by epinephrine, 108 molecules of glucose-1-phosphate!

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Figure 11.17 shows four different cellular results from a single signaling molecule. Briefly describe each response. 1. Cell A: Pathway leads to a single response; 2. Cell B: Pathway branches, leading to two responses. 3. Cell C: Cross-talk occurs between two pathways. 4. Cell D: Different receptor leads to a different response.

42. How do scaffolding proteins enhance a cellular response? •Scaffolding proteins are large relay proteins to which other relay proteins are attached •Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway

Concept 11.5 Apoptosis (programmed cell death) integrates multiple cellsignaling pathways 43. What specifically happens to a cell during the process of apoptosis? •Apoptosis is programmed or controlled cell suicide •A cell is chopped and packaged into vesicles that are digested by scavenger cells •Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

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The signal for apoptosis can come from outside or inside the cell. Give one example when the signal comes from outside the cell and two examples of cellular occurrences that would prompt an apoptosis signal from inside the cell.

Outside: •Apoptosis is important in shaping an organism during embryonic development •The role of apoptosis in embryonic development was first studied in Caenorhabditis

elegans •In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis

Figure 11.20 illustrates this action: Molecular basis of apoptosis in C. elegans originating OUTSIDE the cell.

Inside: •Caspases are the main proteases (enzymes that cut up proteins) that carry out

apoptosis •Apoptosis can be triggered by: 1. An extracellular death-signaling ligand; 2. DNA damage in the nucleus; and 3. Protein misfolding in the endoplasmic reticulum 4. •Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals •Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers e.g. Picture below, effect of apoptosis during paw development in the mouse

Testing Your Knowledge: Self-Quiz Answers

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