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CH 5*, 31*, 32* LO 4.9 1. Why do you communicate? 2. How do you communicate? 3. How do you think cells communicate? 4. Do you think bacteria can communicate? Explain. 1. Compare the structure & function of these receptor proteins: GPCR, tyrosine kinase and ligand-gated ion channels. 2. What is a second messenger? What are some examples of these molecules? 3. What are the possible responses to signal transduction in a cell? CHAPTER 5 The 3 stages of cell communication: reception, transduction, and response. How G-protein-coupled receptors receive signals and start transduction. How receptor tyrosine kinase receive cell signals and start transduction. How a cell signal is amplified by a phosphorylation cascade. How a cell response in the nucleus turns on genes while in the cytoplasm it activates enzymes. What apoptosis means and why it is important to normal functioning of multicellular organisms. Prokaryotes! All types! (but in different ways) Bonnie Bassler on How Bacteria “Talk” https://www.ted.com/talks/bonnie_bassler_on_how_ bacteria_communicate/transcript?language=en 18:14 1. Why are scientists studying how bacteria (and not just human cells) communicate? 2. What is quorum sensing? 3. Describe how Vibrio fischeri use quorum sensing in squid. 4. According to Bonnie Bassler (Princeton University), what are scientists hoping to use as the next class of antibiotics? Animal cells communicate by: Direct contact (gap junctions) Secreting local regulators (growth factors, neurotransmitters) Long distance (hormones) LOCAL VS LONG DISTANCE SIGNALING Local regulators – affect only nearby cells Neurotransmitters released from neurons Direct Contact – between immune cells Hormones – affect distant cells Endocrine signaling – chemicals released into blood and carried throughout body Must have the correct receptors Either inside cell or along cell membrane 1. Reception: Detection of a signal molecule (ligand) coming from outside the cell 2. Transduction: Convert signal to a form that can bring about a cellular response 3. Response: Cellular response to the signal molecule Binding between signal molecule (ligand) + receptor is highly specific. Types of Receptors: a) Plasma membrane receptor water-soluble ligands b) Intracellular receptors (cytoplasm, nucleus) hydrophobic or small ligands Eg. testosterone or nitric oxide (NO) Ligand binds to receptor protein protein changes SHAPE initiates transduction signal G-Protein Coupled Tyrosine Kinase Receptor (GPCR) Ligand-Gated Ion Channels G-Protein Coupled Receptor (GPCR) 7 transmembrane segments in membrane G protein + GTP activates enzyme cell response Tyrosine Kinase Ligand-Gated Ion Channels G-Protein Coupled Tyrosine Kinase Receptor (GPCR) Attaches (P) to tyrosine Activate multiple cellular responses at once Ligand-Gated Ion Channels G-Protein Coupled Tyrosine Kinase Receptor (GPCR) Ligand-Gated Ion Channels Signal on receptor changes shape Regulate flow of specific ions (Ca2+, Na+) G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels 7 transmembrane segments in membrane Attaches (P) to tyrosine Signal on receptor changes shape G protein + GTP activates enzyme cell response Activate multiple cellular responses at once Regulate flow of specific ions (Ca2+, Na+) Cascades of molecular interactions relay signals from receptors target molecules Protein kinase: enzyme that phosphorylates and activates proteins at next level Phosphorylation cascade: enhance and amplify signal small, nonprotein molecules/ions that can relay signal inside cell Eg. cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3) cAMP = cyclic adenosine monophosphate GPCR adenylyl cyclase (convert ATP cAMP) activate protein kinase A Regulate protein synthesis by turning on/off genes in nucleus (gene expression) Regulate activity of proteins in cytoplasm Cytoplasm Response Response may regulate activities Ex: epinephrine signals breakdown of glycogen to glucose Notice the signal amplification! Nuclear Response Signal may trigger products to be made Ex: growth factor signals DNA to make certain proteins needed for growth (transcription - ?) (traits - ?) Specificity of Signals The type of proteins a cell has determine which signals it responds to and how it responds Positive feedback: Oxytocin & childbirth Negative feedback: Insulin/Glucagon & blood-glucose Lipid Hormone Testosterone also good example of different effects of same hormone Protein Hormone Insulin Also good example of effect if goes wrong – diabetes What sort of communication happens in this system? What types of cells are involved? Who do they “talk” to? T-cells require self & non-self copntact Antigen = the part they recognize as foreign Il-1 7 IL-2 used to help activate other cells What type of communication takes place here? Where does the “talking” take place? Neurotransmitters released into synaptic cleft… cause channels to open which passes along the “message” What happens when part of the system goes wrong? Which can get through membrane easily? Which will deliver message faster? Evolutionary Link These pathways are similar among all types of cells, even among very different organisms (including bacteria, yeast, plants, and animals) What does this tell us about these pathways? Why would they have been so important that they evolved so early? http://apbiomaedahs.weebly.com/3d-cell-communication- and-signal-transduction.html http://learn.genetics.utah.edu/content/cells/cell com/ Examples: Diabetes Cholera Autoimmune disease Cancer Neurotoxins, poisons, pesticides Drugs (anesthetics, antihistamines, blood pressure meds) Toxin modifies G-protein Disease acquired by drinking contaminated water (w/human feces) Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin involved in regulating salt & water secretion G protein stuck in active form intestinal cells secrete salts, water Infected person develops profuse diarrhea and could die from loss of water and salts Used as treatment for erectile dysfunction Inhibits hydrolysis of cGMP GMP Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis VIAGRA INHIBITS CGMP BREAKDOWN Cell is dismantled and digested Triggered by signals that activate cascade of “suicide” proteins (caspase) Why? Protect neighboring cells from damage Animal development & maintenance May be involved in some diseases (Parkinson’s, Alzheimer’s) Left: Normal WBC Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”) 1. What type of behavior in animals might be triggered by cold temperatures? 2. What type of behaviors might be triggered in hot temperatures? 3. List 2 examples of negative feedback. List 2 examples of positive feedback. 4. What is the main type of chemical messenger in the endocrine system? The nervous system? Compare & Contrast the nervous system with the endocrine system. (focus on the effects on the body Define neurosecretory cell. What is its function? Give an example of positive and negative feedback in the endocrine system. How do they function? 1. Compare peptide hormones to steroids. 2. Explain how insulin and glucagon work to regulate blood sugar levels. 3. Which glands and hormones respond when your body is under stress? A hormone called ecdysteroid regulates the timing of metamorphosis in this anise swallowtail butterfly. Tropism- any growth response that results in plant organs curving TOWARD or AWAY from stimuli Phototropism- the growth of a plant organ TOWARD light or AWAY from it Important plant hormones: Auxin- simulate cell elongation phototropism & gravitropism (high concentrations=herbicide) Cytokinins-cell division (cytokinesis) & differentiation Gibberellins-stem elongation, leaf growth, germination, flowering, fruit development Abscisic Acid- slows growth; closes stomata during water stress, promote dormancy Ethylene-promote fruit ripening (positive feedback!); involved in apoptosis (shed leaves, death of annuals) 1. Drought (water deficit) Close stoma Release abscisic acid to keep stoma closed Inhibit growth Roll leavesreduce SA & transpiration Deeper roots 2. Flooding (O2 deprivation) Release ethyleneroot cell death air tubes formed to provide O2 to submerged roots A hormone called ecdysteroid regulates the timing of metamorphosis in this anise swallowtail butterfly. Two ways hormones affect target organs. The secretion, target, action, and regulation of at least 3 hormones. An illustration of both positive and negative feedback in the regulation of homeostasis by hormones. Local regulators – affect only nearby cells Paracrine signaling – cells release chemicals to nearby cells Neurotransmitters released from neurons Hormones – affect distant cells Endocrine signaling – chemicals released into blood and carried throughout body Cells can also pass messages directly - Gap junctions - Plasmodesmata - “ID tag” recognition Endocrine System = Hormone-secreting cells + Tissues Endocrine glands: ductless, secrete hormones directly into body fluids Hormones: chemical signals that cause a response in target cells (receptor proteins for specific hormones) Affects 1 tissue, a few, or most tissues in body Or affect other endocrine glands (tropic hormones) Regulation by Positive & Negative Feedback Pheromones Hormones Local Regulators Chemical Chemical signal from Chemical signal from 1 endocrine signal from one individual to gland through cell to an another blood to target adjacent cell individual cell Eg. cytokines, Eg. peptide, Eg. ant trail; sex growth factors, steroid pheromones nitric oxide hormones (NO) https://www.youtube.com/watch?v=-S_vQZDH9hY Peptide Steroid Water-soluble Lipid-soluble Bind to receptors on Enters cell & binds to plasma membrane & triggers signal transduction pathway Affects protein activity already present in cell Rapid response Short-lived Eg. oxytocin, insulin, epinephrine intracellular receptors Causes change in gene expression (protein synthesis) Slower response Longer life Eg. androgens (testosterone), estrogen, progesterone, cortisol 1.Liver cells break 2.Blood vessels to down glycogen and skeletal muscles release glucose dilate 3.Blood vessels to intestines constrict Master Glands Hypothalamus Pituitary Gland Master Glands Hypothalamus • Receives info from nerves and brain • Initiates endocrine signals Posterior pituitary gland: • Oxytocin: contract uterine muscles, eject milk in nursing Pituitary Gland • Antidiuretic Hormone (ADH): promote H2O retention by kidneys Anterior pituitary gland: • Follicle-stimulating hormone (FSH): development of ovarian follicles (eggs); promote sperm production • Luteinizing hormone (LH): trigger ovulation; stimulate testosterone production in testes HYPOTHALAMUS POSTERIOR PITUITARY HYPOTHALAMUS ANTERIOR PITUITARY Negative feedback systems: • Thyroid hormones • Blood Ca2+ levels • Blood glucose levels Positive feedback system: • Oxytocin (birthing process; release of milk/suckling) INSULIN & GLUCAGON High blood glucose Liver breaks down glycogen and releases glucose into blood Insulin released from pancreas Glucagon released from pancreas Body cells take up glucose Liver stores glucose as glycogen Blood glucose drops Type I diabetes (10%):deficiency of insulin Insulin-dependent Autoimmune disorder beta cells of pancreas destroyed Type II diabetes (90%): failure of target cells to respond to insulin Non-insulin dependent Insulin produced cells don’t respond (defect in insulin receptor or response pathway) Risk factors: obesity, lack of exercise Thyroid Gland Hypothalamus Graves’ Disease: Autoimmune disorder TRH Antibodies bind to TSH receptor Anterior pituitary Hyperthyroidism High temp, sweating, weight loss, high BP TSH Thyroid T3 T4 STRESS AND THE ADRENAL GLAND Legally prescribed to treat hormone deficiency, loss of muscle mass (cancer, AIDS) Used to enhance performance and improve physical appearance SOURCE: WWW.DRUGABUSE.GOV/INFOFACTS/STEROIDS.HTML aggression extreme mood swings liver damage jaundice fluid retention high blood pressure increases in LDL (“bad” cholesterol) decreases in HDL (“good” cholesterol) renal failure severe acne For men—shrinking of the testicles, reduced sperm count, infertility, baldness, development of breasts, increased risk for prostate cancer For women—growth of facial hair, male- pattern baldness, changes in or cessation of the menstrual cycle, enlargement of the clitoris, deepened voice For adolescents—stunted growth due to premature skeletal maturation and accelerated puberty changes; risk of not reaching expected height if AAS is taken before the typical adolescent growth spurt In addition, people who inject AAS run the added risk of contracting or transmitting HIV/AIDS or hepatitis. What determines whether a signal will bind to a membrane protein or an intracellular protein? Membrane signals – cannot get through Large - polar - ionic Intracellular signals – can get through Hydrophobic - small Which types of cells communicate this way? Most of them! bacteria – yeast (fungi) – plants - animals Briefly explain the role of each numbered step in regulating target gene expression. (2013 #8)