Cell Communication PDF
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This document provides a comprehensive overview of cell communication, detailing various types such as autocrine, juxtacrine, paracrine, and endocrine signaling. It explains the roles of sending and target cells, and discusses signal transduction pathways in different organisms. The document also touches upon important concepts like quorum sensing and hormones.
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Cell Communication Many groups A specific group Public Analyze this diagram: 1. Describe the role of the sending cell. Creates and releases the ligand (messenger molecule) 2. Describe the role of the target c...
Cell Communication Many groups A specific group Public Analyze this diagram: 1. Describe the role of the sending cell. Creates and releases the ligand (messenger molecule) 2. Describe the role of the target cell. Has the receptor that the ligand binds to and triggers the response 3. Distinguish between the target and non-target cell. Target contains a receptor for the ligand and nontarget does not. Cell Communication is Essential for All Cells ○ Cells must respond to their environment ○ Cells must to coordinate activities in multicellular organisms Important Things to know…………… 1. Chemical signals allow cells to communicate without physical contact. 2. The distance between the signaling cells and the responding cell can be small or large. 3. There is often a gradient response 4. Threshold concentrations are required to trigger the communication pathway. 5. Many signal transduction pathways include: protein modification and phosphorylation cascades. Evolution of cell signaling Microbes (bacteria or fungi) provide a glimpse of the role of cell signaling in the evolution of life. Cells send out external signals that are converted to responses within other cells. Ex: Yeast cells, Saccharomyces cerevisiae, of different mating types, a and 𝛼, locate each other by secreting signaling factors specific to each type. A signal binding to the cell’s surface triggers a signal transduction pathway Schmoo Transduction is a series of steps that leads to a (extension) specific cellular response: Ex: creation of a schmoo to allow for mating Yeast Mating What is Quorum Sensing? 1. Bacteria produce signaling molecules (autoinducers) 2. When enough bacteria are present, called a quorum Quorum 🡪a minimum number of individuals present, the concentration of signaling molecules increases enough for bacteria to sense local population density. 3. At this density, all the bacteria turn on a signal transduction pathway at once. (resulting in bioluminescence, formation of biofilms or toxins) Evolution of Cell Signaling Signal transduction pathways in simple bacteria, in fungi, in plants and in complex animals share molecules and mechanisms of action. Similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes. What is Signal Transduction? Communication in General Reception, Transduction and Response to a signal Self Signaling Autocrine Cell talking to “itself” Direct Signaling Juxtacrine Short Distance Paracrine Long Distance Signaling Endocrine Autocrine signaling - A cell signals to itself. - Cell releases a ligand that binds to receptors on its own surface or inside of the cell. - plays an important role during development, helping cells take on and reinforce their correct identities. - is thought to play a key role in metastasis (spreading of cancer). - Oftentimes, a signal may have both autocrine and paracrine effects, binding to the sending cell as well as other similar cells in the area. Juxtacrine 🡪 Direct Contact Signaling Signaling substances dissolved in the cytosol pass freely between adjacent cells connected by gap junctions or Plasmodesmata. Animal cells = gap junction Plant cells = plasmodesmata Juxtacrine Direct Signaling🡪 Cell to Cell Recognition Immune Cells communicate via direct contact between oligosacharrides (antigens) on their surfaces. “Self from Non-self” Juxtacrine 🡪 Direct Signaling Contact Inhibition Juxtacrine 🡪 Direct Signaling In another form of direct signaling, two Cytokines are small cells may bind to one another because proteins that are crucial in controlling the growth they carry complementary proteins on and activity of other immune system cells and their surfaces. When the proteins bind to blood cells. When released, they signal the one another, this interaction changes the immune system to do its job shape of one or both proteins, transmitting a signal. This kind of signaling is especially important in the immune system, where immune cells use cell-surface markers to recognize “self” cells (the body's own cells) and cells infected by pathogens Juxtacrine 🡪 Direct Signaling Immune System Antibodies are released by B cells. Antibodies mark the foreign cells for destruction. macrophage VIDEO – NPR How Viruses Viruses -> attack a host cell Attack (Youtube – 3:38) Macrophages -> destroy foreign invaders that have their antigens marked by antibodies how COVID enters cells 7min Paracrine Signaling 🡪 Short Distance Examples: Neurotransmitters in Synapse (Synaptic Signaling) Quorum Sensing in Bacteria Yeast Mating Paracrine Signaling 🡪 Short Distance Often, cells that are near one another communicate through the release of chemical messengers (ligands that can diffuse through the space between the cells). This type of signaling, in which cells communicate over relatively short distances, is known as paracrine signaling. Paracrine signaling allows cells to locally coordinate activities with their neighbors. Although they're used in many different tissues and contexts, paracrine signals are especially important during development, when they allow one group of cells to tell a neighboring group of Paracrine Signaling 🡪 Short Distance Synapse Synapses are spaces between neurons and between neurons and receptor or effector cells Communication Across the Synapse Neurons release a chemical messenger, a neurotransmitter, into the synapse to continue the message Presynaptic neuron Postsynaptic neuron neurotransmitters Synaptic signaling One unique example of paracrine signaling is synaptic signaling, in which nerve cells transmit signals. This process is named for the synapse, the junction between two nerve cells where signal transmission occurs. When the sending neuron fires, an electrical impulse moves rapidly through the cell, traveling down a long, fiber-like extension called an axon. When the impulse reaches the synapse, it triggers the release of ligands called neurotransmitters, which quickly cross the small gap between the nerve cells. When the neurotransmitters arrive at the receiving cell, they bind to receptors and cause a chemical change inside of the cell (often, opening ion channels and changing the electrical potential across the membrane). The neurotransmitters that are released into the chemical synapse are quickly degraded or taken back up by the sending cell. This "resets" the system so they synapse is prepared to respond quickly to the next signal. Interesting Neurotransmitters VIDEO: Molly on Your Brain (YouTube - 2:30) Crack is Wack 3min How Do Antidepressants Work? VIDEO: How Do SSRI’s Work? (YouTube - 1:24) Endocrine Signaling 🡪 Long Distance When cells need to transmit signals over long distances, they often use the circulatory system as a distribution network for the messages they send. In long-distance endocrine signaling, signals are produced by specialized cells and released into the bloodstream, which carries them to target cells in distant parts of the body. Signals that are produced in one part of the body and travel through the circulation to reach far-away targets are known as hormones. Endocrine Signaling 🡪 Long Distance Plant Hormone hormones may travel in vessels, but more often travel from cell to cell or by diffusion in air. ex: Ethylene - plant hormone that diffuses through the air and causes fruit to ripen Positive feedback mechanism Different Types of Plant Hormones Click here to learn about Plant Hormones Endocrine Signaling 🡪 Long Distance Specialized endocrine cells release hormones like insulin into the blood stream, by which they travel through the bloodstream to target cells in other parts of the body. Hormones Communicate messages to target cells far away Endocrine Signaling 🡪 Long Distance Hormones regulate positive feedback mechanisms. Bozeman Science - Feedback Loops (YouTube - 14:25) Endocrine Signaling 🡪 Long Distance Hormones regulate negative feedback mechanisms. Autocrine – Cell talking to “itself” Juxtacrine – Direct Contact Paracrine – Short distance “Staying Local” Endocrine – Long distances Ex: Hormones in traveling in Bloodstream What is Signal Transduction? a series of steps by which a signal on a cell’s surface is converted into a specific cellular response. 1. Reception - a chemical signal binds to a cellular protein, typically at the cell’s surface 2. Transduction A shape change occurs, and a signal is sent 3. Response - A specific Cellular response Application Question What would happen if there was a change in the structure of any signaling molecule? - A change in the shape would inhibit the reception thus desrupting the cascade of signal pathway EX: mutations = affect downstream components by altering the subsequent transduction Open 🡪 Feedback Signaling Models Feedback & Signaling Feedback Signal KEY Ligands are Signal Molecules A signal molecule binds to a receptor protein causing the protein to change shape Ligand = small molecule that binds specifically to receptor What happens after the ligand binds to the receptor protein? The receptor protein undergoes a conformational shape change thus activating it. Ligands bind to Signal Receptors Most signal receptors are plasma membrane proteins. Some receptors are inside the cell Why do water soluble (polar) signal molecules need a protein to get through the membrane? Because they are hydrophilic they cannot dissolve through the hydrophobic parts of the cell membrane and therefore must be transported via a membrane protein Signal Receptors Types of receptors Receptors come in many types, but they can be divided into two categories: Surface receptors = found embedded in the plasma membrane. Intracellular receptors =found inside of the cell (in the cytoplasm or nucleus) Intracellular Surface Receptors Receptors Cell Signaling Basics When a ligand binds to a cell-surface receptor, the receptor’s intracellular domain (the part inside the cell) changes in some way. There is a confirmational shape change, which makes it active 🡪 as an enzyme or let it bind other molecules. The change in the receptor sets off a series of signaling events. For instance, the receptor may turn on another signaling molecule inside of the cell, which in turn activates its own target. This chain reaction can eventually lead What is Phosphorylation? What does it actually mean to be on or off? Proteins can be activated or inactivated in a variety of ways. The addition of a phosphate group to one or more sites on the protein, a process called phosphorylation. The transfer of the phosphate group is catalyzed by an enzyme called a kinase. There are many different kinases (enzymes that phosphorylate) Phosphorylation often acts as a switch. Sometimes, phosphorylation will make a protein more active. In other cases, phosphorylation may inactivate the protein or cause it to be broken down. Cell Signaling Pathways BASICS 🡪 Worksheet Answer the following questions based off the figure above; 1. What does “phosphorylate” mean? To add a phosphate to a molecule 2. What does the “-ase” in a protein name signify? -ase means that the protein is an enzyme 3. A type of enzyme is called a kinase. What does a kinase do? A kinase adds a phosphate group (from ATP) to a molecule 4. Another type of enzyme is called a phosphatase. What does a phosphatase do? A phosphatase removes a phosphate group from a molecule This diagram shows part of the epidermal growth factor signaling pathway: Phosphorylation (marked as a P) is important at many stages of this pathway. When growth factor ligands bind to their receptors, the receptors pair up and act as kinases, attaching phosphate groups to one another’s intracellular tails. The activated receptors trigger a series of events (skipped here because they don't involve phosphorylation). These events activate the kinase Raf. Active Raf phosphorylates and activates MEK, which phosphorylates and activates the ERKs. The ERKs phosphorylate and activate a variety of target molecules. The activated targets promote cell growth and division. Secondary messengers Although proteins are important in signal transduction pathways, other types of molecules can participate as well. Many pathways involve second messengers, small, non-protein molecules that pass along a signal initiated by the binding of a ligand (the “first messenger”) to its receptor. Secondary Messengers : Ca+2 cAMP, a derivative of ATP cGMP Amplification MaK IP3 - inositol triphosphate, which are made from phospholipids. For example, the ligand acetylcholine causes opposite effects in skeletal and heart muscle because these cell types produce different kinds of acetylcholine receptors that trigger different pathways Practice Cell Signaling Questions B C A Muscular relaxation = Arteries relax/dilate 🡪 Penis fills with blood Identify the first messenger that starts the signal transduction in the smooth muscle cell. Nitric oxide (NO) What is the likely second messenger? There are actually two secondary messengers apparent in the figure, cGMP and Ca 2+ Identify the cellular response caused by the cell signaling cascade. Muscle relaxation Explain why the arrows go from small to bigger. This is an example of signal amplification. The signal starts small with a few nitric oxide molecules and gets bigger/amplifies as it moves down the signal transduction pathway. Identify whether the receptor that starts the cell signaling pathway is in the plasma membrane or intracellular. The nitric oxide (NO) crosses the cell membrane and then activates the guanylyl cyclase, so it is in the intracellular. This makes sense because NO is small and non-polar, able to cross the cell membrane. Ginseng Viagra Assignment 2 1. Knowing that Melody said ginseng enhances erection, what effect would you expect ginseng to have on nitric oxide(NO)? Why? You need to be able to see that more NO would activate more guanylyl cyclase, creating more cGMP and eventually leading to erection. So ginseng must somehow increase NO. If it decreased NO, then there wouldn’t be any NO to turn on the cell signaling pathway leading to erection. 2. Knowing that Melody said Viagra also enhances erection, what effect would you expect it to have on PDE5? Why? This one is more complicated. You must make the connection that PDE5 breaks down cGMP, which is important in turning on PKG, which eventually leads to erection. So the Viagra must block activity of PKG, enhancing the effectiveness of the cGMP that is present. 3. If neither chemical works, what protein(s) would you suspect is “broken”? Most of my class can’t pinpoint exactly which protein is broken; they should assume that it is a protein downstream from GC and PDE5. Nitric oxide (NO) is a gas that acts as a ligand. Like steroid hormones, it can diffuse directly across the plasma membrane thanks to its small size. One of its key roles is to activate a signaling pathway in the smooth muscle surrounding blood vessels, one that makes the muscle relax and allows the blood vessels to expand (dilate). In fact, the drug nitroglycerin treats heart disease by triggering the release of NO, dilating vessels to restore blood flow to the heart. NO has become better-known recently because the pathway that it affects is targeted by prescription medications for erectile AP/IB Biology - FRQ The figure below represents a generalized hormone-signaling pathway. Briefly explain the role of each numbered step in regulating target gene expression. (3pts) Step 1 Signal Reception. The Ligand is the signal, and it binds to a receptor protein typically embedded in membrane. There is a conformational shape change in the receptor. A ligand can be a hormone or a neurotransmitter. (1pt) Step 2 is Transduction. The signal is transmitted as cascade response. Most likely there are Kinases that phosphorylate to promote the cascade. (1 pts) Step 3 is the response. The transcription factor is activated. This can turn on a gene to make a protein or it can turn off a gene (1pt) Three Types of Signal Receptors 1. G-protein-coupled receptors (GPCR) 2. Tyrosine-kinase receptors (TKR) 3. Ion-channel receptors. G-Protein Coupled Receptors (GPCR) 1. A G-protein coupled receptor (GPCR) consists of a receptor protein associated with a G-protein. 2. What’s a G-protein? A family of proteins involved in chemical signals outside the cell causing changes inside the cell. Involves GTP and GDP 3. Examples? GPCRs are receptors for hormones and neurotransmitters G-Protein Coupled Receptor (GPCR) G-protein-coupled receptors are transmembrane proteins consisting of seven alpha helices spanning the membrane. How does a GPCR work? 1. The signal molecule binds to the receptor’s binding site on the outside of the cell. This activates the receptor. 2. The G-protein is activated. 3. The activated G-protein activates a cascade of further compounds (often times an enzyme) and causes a change downstream in the cell. Signal Transduction Animation 2.5min G proteins come in different types, but they all bind the nucleotide guanosine triphosphate (GTP), which they can break down (hydrolyze) to form GDP. A G-protein attached to GTP is active, or “on,” A G-protein that’s bound to GDP is inactive, or “off.” The G proteins that associate with GPCRs are a type made up of three subunits, known as heterotrimeric G proteins. When they’re attached to an inactive receptor, they’re in the “off” form (bound to GDP) The G-Protein acts as an “on-off” switch ○ If GDP is bound, the G protein is inactive. ○ If ATP or GTP is bound, the G protein is active. ○ The G-protein system cycles between off and on “OFF” G-Protein Coupled Receptor (GPCR) “OFF” “ON” G-Protein Coupled Receptor (GPCR) BACK TO “OFF” Khan Academy Cell Signaling 6min Amplification (WATCH SEVERAL TIMES) G-Protein Coupled Receptor (GPCR) Epinephrine Adrenaline Action of epinephrine to GPCR through translation of protein (Youtube – 1:50) VIDEO - Signal Transduction Animation (YouTube - 2:32) Steps in G-Protein Coupled Receptors with Epinephrine GPCR (Jack) 1. Ligand binds to GPCR RECEPTION TRANSDUCTION 2. GPCR undergoes a conformational shape change and binds to G-protein. = ACTIVATES THE RECEPTOR 3. Alpha subunit exchanges GDP for GTP 4. Alpha subunit dissociates and binds to and activates the target protein. For epinephrine, the target protein is the enzyme adenylate cyclase. 5. The target protein (adenylyl cyclase) can relay a second messenger (cAMP). The secondary messenger (cAMP) continues the cascade of reactions. (i.e. binds to protein kinase-A, which activates the enzyme phosphorylase, which converts glycogen to glucose) Response 6. A response occurs –Epinephrine produces an enzyme that breaks down glycogen to glucose. 7. GTP is hydrolyzed to GDP which inactivates the G protein once the response occurs Use the following information and the diagram above to answer the questions; G-protein-coupled receptors have roles in the following Visual sense (rhodopsin) Sense of smell (olfactory receptor) Behavioral and mood regulation (serotonin, dopamine, GABA, glutamate) Immune system activity and inflammation (chemokine receptors, histamine receptors) Autonomic nervous system receptors Apoptosis ~45% of all pharmaceutical drugs are known to target GPCRs G-protein-coupled receptor has a system that consists of two parts. Describe the receptor and the G protein (color in diagram, size, location, etc.). Receptor (light blue) is a large integral protein that has an extracellular hydrophilic domain for binding to the signaling molecule and a transmembrane hydrophobic domain for stabilizing its position within the membrane. The G-protein (pink) is a small peripheral protein associated with the GPCR. Based on what you know about ATP, what do you think GTP is/what it stands for? GTP is guanosine triphosphate, a high-energy molecule with three phosphate groups. Once activated, the G protein moves and activates another enzyme. In the case of the diagram, what enzyme is being activated? Adenylyl cyclase is the enzyme that is activated by the activated G-protein. What is the second messenger that is being created? cAMP is the second messenger that is created by adenylyl cyclase G-Protein-Linked (Coupled) Receptor (GPCR) G-Protein-Linked (Coupled) Receptor (GPCR) Summarized: Ligand binds to receptor (RECEPTION) Receptor undergoes a conformational change ION) UC T (changes shape) activating it N S D T R A GDP → GTP activating the G-protein ( Sets in motion a cascade of reactions, which includes a second messenger, that results in a cellular response (RESPONSE) Play again 🡪 Action of Epinephrine on a Liver Cell G-Protein-Linked (Coupled) Receptor (GPCR) Why should I care about GPCR? Your vision and smell senses use G-protein-coupled receptors. Diseases like botulism, pertussis (whooping cough), and cholera produce toxins that interfere with GPCRs. Around 60% of medicine works by affecting GPCRs, and a whole lot of drugs (including heroin) work the same way. GPCR (only play to 1.5 min The response of a particular cell to a signal depends on its particular collection of receptor proteins, relay proteins, and proteins needed to carry out the response. (Remember: many effects of epinephrine on different types of cells) The Tyrosine-Kinase Receptor The tyrosine-kinase receptor system is especially effective when the cell needs to regulate and coordinate a variety of activities and trigger several signal pathways at once. The cytoplasmic side of these receptors function as a tyrosine kinase, transferring a phosphate group from ATP to tyrosine on a protein. The Tyrosine-Kinase Receptor Components: 1. an extracellular signal-binding sites 2. a single alpha helix spanning the membrane 3. an intracellular tail with several tyrosines. The Tyrosine-Kinase Receptor How does it work? 1. When 2 ligands (signal molecules) bind to 2 receptor proteins, the polypeptides come together, forming a dimer. 2. This activates the tyrosine-kinase section of both. 3. Each protein adds phosphates (from ATP) to the tyrosine tails of the other polypeptide. The Tyrosine-Kinase Receptor 4. The fully-activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules. 5. These activated relay proteins trigger many different transduction pathways and responses. (cascade of reactions) SAMPLE The Tyrosine-Kinase Receptor CLAYMATION Examples of signal molecules that bind to tyrosine kinase receptors: Insulin Growth factors (that control cell division) ANIMATION - Receptor Tyrosine Kinases (Newer Version) (YouTube - 4:38) ANIMATION - Cell Signaling- Tyrosine Kinase receptors (Youtube – 5:33) The Tyrosine-Kinase Receptor Once signals are received, transduction is initiated and a series of reactions occurs like falling dominoes. Let’s break down the name “receptor tyrosine kinase.” What is a receptor? A molecule that a specific ligand/signaling molecule binds to. What is tyrosine? a kind of amino acid What is a kinase? What molecule is phosphorylated? An enzyme that adds a phosphate to another molecule. The intracellular domain of the receptor is phosphorylated. Is the ligand-binding site an extracellular region, is it in the membrane, or is it intracellular?Extracellular region What does “dimerize” mean? Two molecules come together as one unit. Describe what is happening in each of the four steps in the diagram. 1. The signal binds to the extracellular binding site on the receptor tyrosine kinase 2. When two neighboring receptors have bound to the signal, they come together, or dimerize. 3. Each of the receptor dimers phosphorylates the other in a process called autophosphorylation. This involves the intracellular domains of the two receptors. 4. The phosphorylated receptors then activate relay proteins by phosphorylating them (hence the name “kinase”) Answer the following questions based off the figure. The image shows a phosphorylation cascade. What do you think this means? A series of events where the activation of one protein leads to the phosphorylation of another, which activates that molecule to phosphorylate the next molecule in the series of events. This next molecule is then activated to phosphorylate yet another molecule until the final molecule is activated to produce the response. Explain how this transduction pathway shows an amplification event. Each step of the pathway shows an increase in the concentration of molecules. Binding of 1 signal molecule results in millions of active end-product enzymes What type of receptor is epinephrine binding to? G-protein coupled receptor (GPCR) What type of molecule does adenylyl cyclase make? The second messenger cAMP What is the response that results from epinephrine binding to this particular receptor? Breakdown of glycogen into glucose 1-phosphate. The glucose can be used in the Answer the following questions based off the figure on “Epidermal Growth Factor”; Based on this pathway, is EGF a steroid or a peptide hormone? Peptide hormone because it does not cross the membrane State the ligand in this pathway. Epidermal growth factor (EGF) Based on this pathway, what type of receptor is the EGF receptor? a) ligand-gated ion channel b) tyrosine kinase receptor c) G-protein-coupled receptor What are the main target (end) proteins of the EGF signaling pathway? What will happen to the cell after this pathway is activated? C-Myc, which acts as a The cells grow and divide transcription factor The Tyrosine-Kinase Receptor Summarized: 2 Ligands (ex: 2 insulin) bind to receptor Receptor changes shape 🡪 dimer = dimer is phosphorylated = now it’s fully activated The ATP phosphorylates the dimer triggering a cascade (phosphorylation cascade) of reactions which causes a response The Tyrosine-Kinase Receptor The Islets of Langerhans in the pancreas produces two hormones: Insulin Glucagon The Tyrosine-Kinase Receptor The Islets of Langerhans in the pancreas produces two hormones: 1. Insulin Tyrosine Kinase Receptor From beta (β) cells Decreases blood glucose levels 2. Glucagon GPCR From alpha (α) cells Increases blood glucose levels The Tyrosine-Kinase Receptor Cell Signaling Pathway of Insulin Transduction: BindingResponse: increased of the signaling cellular molecule Reception: Insulin binds alters to a the receptor. uptake An activeofdimer glucose and when forms increased production of glycogen a seriesfrom tyrosine kinase receptor on occurs. phosphorylation This starts of glucose in the liver and muscles. the cell surface. changes in other molecules. This GIF is slow. **Watch the whole thing – glucose enters the cell The Tyrosine-Kinase Receptor Cell Signaling Pathway of Insulin The Tyrosine-Kinase Receptor What happens when the tyrosine-kinase receptors are inactivated? Diseases occur such as – diabetes – Alzheimer’s disease – multiple sclerosis – cystic fibrosis The Tyrosine-Kinase Receptor What happens when the tyrosine-kinase receptors are overactivated? Cancer (uncontrolled cell growth) Ligand-Gated Ion Channels Protein pores that open or close in response to a chemical signal Ligand binds on extracellular side -> protein’s shape changes and the channel opens Ion flow occurs -> concentration and charge changes inside the cell Ligand-Gated Ion Channels Play a vital role in the nervous system (think back to axon of neurons) Ligand Gated channels and GPCRs 2 min Ligands That Diffuse Through the Membrane Some signal receptors are in the cytosol or nucleus of target cells. EX: nitrous oxide (NO) ○ Small ○ Gas ○ Helps blood vessels expand and contract ○ Keeps blood flowing and free from clots Ligands That Diffuse Through the Membrane Some hormones diffuse through the membrane ○ Hydrophobic hormones (steroids) Aldosterone Testosterone Transcription Factor Progesterone The receptor for these ligands are in the cytoplasm. These activated receptor proteins enter the nucleus and turn on genes that control male sex What are transcription factors? Control which genes are turned on Which genes are transcribed into mRNA 🡪 protein Some of these factors are activators (increase expression) while others are repressors (decrease expression) Gene regulation explains the differences between organisms with similar genes. Second Messengers What are second messengers? Small, nonprotein, water- soluble molecules or ions Diffuse rapidly throughout the cell Many hormones trigger the formation of cAMP in the signal response McGraw Hill MAK second Messenger Second Messengers Participate in pathways initiated by both GPCR and tyrosine-kinase receptors EX: cAMP, cGMP, Inositol Triphosphate and Ca2+ (and others) Animal cells - increases in Ca2+ 🡪 contraction of muscles Plant cells - increases in Ca2+ 🡪 trigger responses for coping with environmental stresses (interactions with pathogens, drought, pollution, changing temperatures) Ligand type Hydrophilic/Protein Hydrophobic/Lipid steroid Cross membrane? No Yes Location of receptor On membrane (transmembrane In cytoplasm or nucleus protein) Type of action Stimulates a signal transduction Combination of receptor pathway, often using second & signal acts as a messengers. transcription factor Duration of action Short (measured in minutes or Long (measured in weeks hours) or years) Examples -Protein hormones Steroid hormones insulin, (estrogen, testosterone, glucagon, progesterone), thyroid epinephrine/ adrenaline hormones, Nitrous oxide -neurotransmitters (acetylcholine) Tell the story of both pathways Apoptosis What is apoptosis? Programmed cell death How does it occur? Triggered by molecular signals that activate a cascade of “suicide” proteins in cells destined to die. VIDEO: Apoptosis (YouTube - 3:58) Apoptosis What happens during apoptosis? Cell shrinks, the nucleus condenses, and the DNA is fragmented. Phagocytic cells engulf and digest the membrane- bound remains by phagocytosis. ANIMATION – Apoptosis (Youtube – 4:38 ) Apoptosis Why is apoptosis so important for normal functions? Necessary for normal development and differentiation Disruption of normal apoptotic processes can lead to ○ webbed fingers/toes in human hands and feet. ○ immune dysfunction ○ certain cancers Apoptosis Apoptosis is key to homeostasis and is a primary example of cell signaling within various organisms. 10 Practice Cell Communication MCQ Answer: A 1. During an experiment, researchers introduced a substance that caused the Class I MHC molecule to break down. Which of the following best describes how the cell-mediated immune response will be affected? A. The killer T-cell will no longer bind to the infected cell, and as a result, the infected cell will not be killed. B. The killer T-cell will no longer bind to the infected cell, and the infected cell will instead be killed by killer T-cells releasing long-distance signals. C. The killer T-cell will still bind to the infected cell, but the infected cell will instead be killed by a helper T-cell. D. The killer T-cell will still bind to the infected cell, but the infected cell will not be killed. 2. Since the discovery in 1960s, a cell–cell signaling system known as quorum sensing (QS) has been identified in numerous microbial species. During cell growth, small signaling molecules are synthesized and secreted into the surrounding environment. As a result, the local QS signal concentration increases with cell density. When the cell density is above a certain threshold, a significant amount of signaling molecules bind to intracellular or membrane receptors and trigger the expression of a series of genes to control a wide spectrum of phenotypes.Some microbes use QS signaling pathways to trigger the expression of virulence genes. The expression of these genes enhances the virulence, or harmfulness, of the microbial infection. Which of the following represents the best method to decrease the virulence of a microbe capable of QS? A. Develop a drug that decreases the cell density needed to express virulence genes. B. Develop a drug that increases the binding of QS signaling molecules to their receptors. C. Develop a drug that decreases the cell density of the microbial infection. D. Develop a drug that increases the cell density of the microbial infection. Answer: C 3. Which of the following best describes the cell communication occurring in the figure to the left? A. A signal-emitting cell communicates with a far-away cell by releasing long-distance signaling molecules. B. A signal-emitting cell communicates with a nearby cell through direct cell-to-cell contact. C. A signal-emitting cell communicates with a far-away cell by releasing local regulators. D. A signal-emitting cell communicates with a nearby cell by releasing local regulators. Answer: D Activated B-Cell 4. During an experiment, researchers introduced a substance that caused the T-cell receptor to break down. Which of the following best describes how the humoral immune response will be affected? A. The helper T-cell will still bind to the B-cell, but the B-cell will not be activated. B. The helper T-cell will still bind to the B-cell, but the B-cell will instead be activated by a killer T-cell. C. The helper T-cell will no longer bind to the B-cell, and as a result, the B-cell will not be activated. D. The helper T-cell will no longer bind to the B-cell, and the B-cell will instead be activated by helper T-cells releasing long-distance signals Answer: C 5. The plant cell wall is a barrier to virus exit from and entry into cells. Thus, successful infection requires that plant viruses encode movement proteins to transport the viral genome locally cell-to-cell within a leaf and on into the vascular system, through which the virus will systematically invade the plant. Which of the following best predicts how movement proteins help plant viruses travel from one plant cell to another? A. Movement proteins increase the surface area of plasma membranes between plant cells. B. Movement proteins increase the movement of transport vesicles between plant cells. C. Movement proteins increase the movement of vacuoles between plant cells. D. Movement proteins increase the permeability of the plasmodesmata between plant cells Answer: D 6. After MEK is activated, it phosphorylates and activates ERK. ERK goes on to phosphorylate and activate a variety of target molecules, including transcription factors like c-Myc that promote cell growth and division. Which of the following toxins will most likely inhibit the phosphorylation of c-Myc? A. A toxin that prevents the phosphorylation of ERK B. A toxin Answer: A the dephosphorylation activity of MEK that prevents C. A toxin that prevents the removal of a phosphate group from ERK D. A toxin that prevents c-Myc from activating ERK The following excerpt and image come from a scientific paper written by Ebrahimi & Chess. They discuss the role of G proteins in olfaction, or the sense of smell. Each mammalian olfactory neuron appears to use the same machinery for transducing signals from its odorant receptor molecules. Upon odorant binding, the receptor is thought to activate GOLF, a G protein. GOLF-mediated activation of adenylate cyclase III then raises intracellular cAMP levels, causing a cyclic-nucleotide-gated channel to open. The influx of cations through this channel ultimately leads to the formation of an action potential, which allows the primary neuron to signal to the brain. A mutation within a component of this signal transduction pathway prevents the activation of GOLF. 7a] Which of the following scientific questions would best help researchers determine how the mutation prevents the activation of GOLF? A. Does the mutation prevent the entry of cations through the cyclic-nucleotide-gated channel? B. Does the mutation prevent ligand binding on the odorant receptor? C. Does the mutation prevent the conversion of ATP to cAMP? D. Does the mutation prevent the activity of adenylate cyclase III? Answer: D. Not B b/c the ligans can bind but the mutation can still not activate the g-protein. (hard question) Answer: D 8. The information below shows and describes the initial steps of the MAPK/ERK signaling cascade. When epidermal growth factor (EGF) ligands bind to their receptors, the receptors pair up and act as kinases, attaching phosphate groups to one another’s intracellular tails. The activated receptors then trigger a series of events that activate the kinase Raf. Which of the following toxins will most likely inhibit the activation of MEK? A. A toxin that prevents the transfer of a phosphate group to Raf B. A toxin that prevents MEK from phosphorylating Raf A or C C. A toxin that prevents the kinase activity of Raf D. A toxin that prevents the dephosphorylation activity of Raf Insulin is a protein hormone that is secreted in response to elevated blood glucose levels. When insulin binds to its receptors on liver cells, the activated receptors stimulate phosphorylation cascades that cause the translocation of glucose transporters to the plasma membrane. Based on the information provided, which of the following best describes the role of insulin in this liver cell signal transduction pathway? (A) It acts as a ligand. Answer: A (B) It acts as a receptor. (C) It acts as a secondary messenger. (D) It acts as a protein kinase. The image above depicts the signal transduction pathway of epinephrine. During one step in the pathway, the enzyme glycogen synthase is phosphorylated, which inactivates the enzyme. If a toxin prevents the phosphorylation of glycogen synthase during this pathway, which of the following will most likely occur when epinephrine comes into contact with its receptor? A. Adenylyl cyclase will be unable to catalyze the conversion of ATP to cAMP. B. The epinephrine receptor will no longer recognize epinephrine. C. Glycogen phosphorylase will phosphorylate glycogen synthase to prevent new glycogen from being made D. Glycogen breakdown will still occur, but glycogen synthesis will not be affected. Answer: D Review Resources PREZI – Reviews Cellular Communication Unit ANIMATION - shows how a G-protein coupled receptor can cause a cell to open a membrane cation channel via second messengers VIDEO - DNALC explains cell signaling (14:15) FRQ 1 molecule B is the ligand/binds to the receptor and activates the receptor/the signaling pathway.