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CAMPBELL & REECE CHAPTER 11 CELL COMMUNICATION

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Cell Messaging some universal mechanisms of cellular regulation cells most often communicate with other cells by chemical signals

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Evolution of Cell Signaling Yeast: Saccharomyces cerevisia 2 sexes: a & type a secrete a signaling molecule called a factor which can bind to receptor proteins on cells @ same time cells secrete factor which binds to receptor proteins on type a cells

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Saccharomyces cerevisiae 2 mating factors then cause the 2 yeast cells to grow toward each other & initiate other cell changes results in fusion or mating of 2 cells of opposite type a/ cell that contains genes of both original cells this new cell later divides passing this genetic combination to their offspring

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Signal Transduction Pathway series of steps initiated by signal molecule attaching to receptor mechanism similar in yeasts and mammals & between bacteria and plants Scientists think signaling mechanisms 1 st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants

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Communication Among Bacteria quorum sensing: bacteria release small molecules detected by like bacteria: gives them a sense of local density of cells allows them to coordinate activities only productive when performed by given # in synchrony ex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)

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Biofilm Developing

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Biofilm Development

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Local Signaling (eukaryotic cells can also use cell junctions) secretion of chemicals = messenger molecules from signaling cell messenger molecules that travel to nearby cells only called: local regulators

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Local Regulators Animals: use 1 class of local regulators: growth factors many cells in neighborhood respond to growth factor produced by 1 cell paracrine signaling: secreting cell acts on nearby target cells by discharging local regulator

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Paracrine Signaling

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Synaptic Signaling in the animal nervous system action potential travels thru cell membrane of neuron when the electrical signal reaches axon end it triggers exocytosis of neurotransmitter (messenger molecule) neurotransmitter travels across small space (synapse) attaches to receptors on target cell

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Synaptic Signaling

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Local Signaling in Plants not as well understood as in animals use hormones (as do animals): long distance signaling aka endocrine signaling travel target cells (any cell that has receptor for hormone) Plant hormones aka plant growth regulators most reach their targets by moving cell-to- cell some travel in vessels

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Long Distance Signaling hormones (in some cases) neurotransmitters: electrical signal travels length of neuron, may go from neuron-to- neuron for long distances ability for any cell to respond to messenger molecule requires cell to have receptor for that particular molecule

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3 Stages of Cell Signaling 1. Reception target cells detection of the signal 2. Transduction receptor protein changes converting signal to a form that can bring about specific cellular response via a signal transduction pathway 3. Response activation of cellular response

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Stages of Cell Signaling Response

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Reception cells must have a receptor for the ligand (messenger molecule) to react with many signal receptors are transmembrane proteins with water-soluble ligands ligands: usually large hydrophilic

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Membrane Receptors

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G-Protein-Coupled Receptors cell-surface transmembrane receptor works with help of a G protein (protein that binds to GTP) flexible inherently unstable difficult to crystallize so can study structure (use x-ray crystallography)

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G Protein-Coupled Receptor: 7 helices

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Receptor Tyrosine Kinases major class of membrane receptors w/enzyme activity kinase: enzyme that catalyzes addition of phosphate group cytoplasmic side of receptor has enzyme that: phosphate group from ATP tyrosine (on substrate protein)

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Tyrosine

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Inactive Monomers of Tyrosine Kinase When there is no ligand attached to receptor site the kinase receptor protein exists as monomers

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Binding of Signaling Molecule: Form Dimers

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Tyrosine Kinase Activated by Dimerization phosphate group added to each tyrosine

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Recognition by Relay Proteins Relay proteins attach to phosphorylated tyrosine structural change that activates the bound protein Each activated relay protein triggers different transduction pathway specific cellular response

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ION CHANNEL RECEPTORS Ligand-Gated Ion Channels

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Ligand Binds to Receptor Site ion crosses membrane & enters cytoplasm transduction pathway leading to a response

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Ligand Dissociates from Receptor Site

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Intracellular Receptors in cytoplasm or nucleus of target cells hydrophobic or very small ligands examples steroid hormones & thyroid hormones of animals NO (nitric oxide), a gas

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Turning on Genes special proteins called transcription factors control which genes are turned on example: Testosterone (steroid hormone) its activated receptor acts as transcription factor that turns on specific genes thus activated receptor carries out transduction of the signal

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TRANSDUCTION when receptors for signaling molecules are membrane proteins the transduction stage is multistep pathway usually involves inactive/active state by adding/removing phosphate group benefit of multistep pathway is that possibility of amplification of signal if each step on pathway can transmit signal to several molecules end up with large # activated molecules @ end of pathway

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Signal Transduction Pathway in most cases original signaling molecule does not enter cell & is not passed along signaling pathway 1 st step triggered by signaling molecule binding to receptor proteins often used as relay molecules (protein interaction a unifying theme of all cellular regulation)

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Protein Phosphorylation & Dephosphorylation protein kinase: enzyme that transfers phosphate groups from ATP protein most act on proteins different than themselves most act on a.a. serine or threonine (not tyrosine as in previous example) includes kinases in plants, animals, & fungi many relay molecules in pathway are kinases

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Phosphorylation Cascade

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Protein Phosphatases enzymes that can rapidly remove phosphate groups from proteins (inactivating them) also make kinases available to reuse this phosphorylation/dephosphorylation system acts as molecular switch in cell position of the switch @ any given time depends on balance between active kinase & active phosphatase molecules

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Second Messengers many signaling pathways involve small, nonprotein, water-soluble molecules or ions known as 2 nd messengers 1 st messenger is extracellular signaling molecule 2 most widely used 2 nd messengers are cAMP & Ca++

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Cyclic AMP epinephrine causes glycogen in hepatocytes to glucose w/out entering cells search for 2 nd messenger that transmits signal from plasma membrane metabolic pathway in cytoplasm epinephrine binding to receptor followed by elevation of cytosolic concentrations of cAMP

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cAMP

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ATP cAMP

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Adenylyl Cyclase enzyme embedded in plasma membrane ATP cAMP in response to extracellular signals directly or indirectly(epinephrine one of many) indirectly: receptor protein changes when signaling molecule attaches activates many adenylyl cyclase possibly thru GTP

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GTP

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cAMP as 2 nd Messenger 1 st messenger activates G protein-coup- led receptor adenylyl cyclase ATP to cAMP activates another protein (usually protein kinase A)

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Protein Kinase A serine/threonine kinase once activated it will phosphorylate other proteins (depends on cell type)

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Other Regulation Mechanisms G protein systems inhibit adenylyl cyclase uses different signaling molecule & receptor

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understanding role of cAMP helps to explain how certain microbes cause disease Vibrio cholerae: causes cholera in contaminated water forms biofilm over small intestines produces a toxin: enzyme that chemically modifies a G protein involved in regulation of water & salt secretion (GTP --/ GDP so protein stays stuck in active form) high [cAMP] cells secrete large amts salts followed by water (osmosis)

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Vibrio cholerae

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Calcium Ions many signaling molecules induce responses in target cell using signal transduction pathways that increase intracellular [Ca++] more widely used than cAMP as 2 nd messenger

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Animal Cells Plant Cells contraction secretion cell division pathway that leads to greening in response to light Effects of Ca++

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Ca++ Concentration Gradient normally, [Ca++] inside cell

Controlling Response generally, response controlled @ >1 site (not just either on or off) 4 aspects of fine-tuning response: 1. Signal amplification 2. Specificity 3. Efficiency 4. Termination of signal

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Signal Amplification enzyme cascades amplify the cells response to a signal @ each step the # of activated products much > in preceding step of cascade amplification happens because activated protein kinase stays in activated form long enuf to process numerous molecules of substrate as result a small # signal molecules (like epinephrine) can release 100s of millions of final product (glucose molecules)

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Specificity of Cell Signaling & Coordination of the Response certain cells respond to some signals & have no response to others 2 different cells may have different responses to same signal different kinds of cells turn on different genes so different kinds of cells have different collections of proteins

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What controls responses in cells? response of a particular cell to a signal depends on its particular collection o 1. signal receptor proteins 2. relay proteins 3. proteins necessary to carry out the response

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Signaling Efficiency: Scaffolding Proteins & Signaling Complexes Scaffolding Proteins: type of large relay protein to which several other relay proteins are simultaneously attached increasing the efficiency of signal transduction

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Scaffolding Proteins Respond to same Signal

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Scaffolding Proteins some are permanently held together (terminal axons in neurons)

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Relay Proteins that are Branch Points Wiskott-Aldrich Syndrome (WAS) defect in single relay protein leads to: abnl bleeding eczema predisposition to: infections leukemia

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Termination of the Signal ability of cell to respond to new signals depends on reversibility of changes produced by prior signals binding of signal molecules to receptors is reversible as [signal molecules] decreases fewer receptor sites occupied by signal those unoccupied: receptor molecule reverts to its inactive form

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Termination of Signal any particular cell response occurs only when concentration of occupied receptors has reached a certain threshold: if below threshold the cell response stops relay molecules return to inactive form cAMP AMP phosphorylated kinases lose phosphate group

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Apoptosis integrates multiple cell- signaling pathways apoptosis: programmed cell death Steps: 1. DNA gets copped up into pieces 2. organelles & other cytoplasmic components fragment 3. cells parts put into vesicles which are engulfed by phagocyctic cells 4. blebbing occurs (cell becomes multilobed)

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Apoptosis in Soil Worm C. elegans 2 genes identified Ced4 & Ced3 (ced for cell death) both encode for proteins essential for cell death are always present in a cell in inactive form C. elegans has protein in outer mitochondrial membrane called Ced9 (from gene of same name) which serves as master regulator of apoptosis (has its brake on until death signal overrides it)

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Signals that Trigger Apoptotic Pathways capase: group of proteins that mediate apoptosis several different pathways involving 15 capases identified in mammals which pathway used depends on type of cell & signal used 1 major pathway involves mitochondrial proteins that form pores in mitochondrial membrane releasing mitochondrial proteins, including cytochrome c, activate capases

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