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CELL COMMUNICATION. Campbell & reece Chapter 11. Cell Messaging. some universal mechanisms of cellular regulation cells most often communicate with other cells by chemical signals. Evolution of Cell Signaling. Yeast: Saccharomyces cerevisia 2 sexes: a & α - PowerPoint PPT Presentation



Campbell & reeceChapter 11CELL COMMUNICATIONCell Messagingsome universal mechanisms of cellular regulationcells most often communicate with other cells by chemical signals

Evolution of Cell SignalingYeast: Saccharomyces cerevisia2 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 cellsSaccharomyces cerevisiae2 mating factors then cause the 2 yeast cells to grow toward each other & initiate other cell changesresults 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 offspringSignal Transduction Pathwayseries of steps initiated by signal molecule attaching to receptormechanism similar in yeasts and mammals & between bacteria and plantsScientists think signaling mechanisms 1st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants

Communication Among Bacteriaquorum 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 synchronyex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)Biofilm Developing

Biofilm Development

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 regulatorsLocal RegulatorsAnimals: use 1 class of local regulators: growth factorsmany cells in neighborhood respond to growth factor produced by 1 cellparacrine signaling: secreting cell acts on nearby target cells by discharging local regulatorParacrine Signaling

Synaptic Signalingin the animal nervous systemaction 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 cellSynaptic Signaling

Local Signaling in Plantsnot as well understood as in animalsuse hormones (as do animals): long distance signaling aka endocrine signalingtravel target cells (any cell that has receptor for hormone)Plant hormones aka plant growth regulatorsmost reach their targets by moving cell-to-cellsome travel in vesselsLong Distance Signalinghormones (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

3 Stages of Cell SignalingReception target cells detection of the signalTransductionreceptor protein changes converting signal to a form that can bring about specific cellular response via a signal transduction pathwayResponse activation of cellular response

Stages of Cell Signaling Response

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

G-Protein-Coupled Receptorscell-surface transmembrane receptorworks with help of a G protein (protein that binds to GTP)flexible inherently unstabledifficult to crystallize so can study structure (use x-ray crystallography)G Protein-Coupled Receptor: 7 helices

Receptor Tyrosine Kinasesmajor class of membrane receptors w/enzyme activitykinase: enzyme that catalyzes addition of phosphate groupcytoplasmic side of receptor has enzyme that: phosphate group from ATP tyrosine (on substrate protein)


Inactive Monomers of Tyrosine Kinase

When there is no ligand attached to receptor site the kinase receptor protein exists as monomersBinding of Signaling Molecule: Form Dimers

Tyrosine Kinase Activated by Dimerizationphosphate group added to each tyrosine

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

ION CHANNEL RECEPTORSLigand-Gated Ion Channels

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

Ligand Dissociates from Receptor Site

Intracellular Receptorsin cytoplasm or nucleus of target cellshydrophobic or very small ligandsexamplessteroid hormones & thyroid hormones of animalsNO (nitric oxide), a gas

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

TRANSDUCTIONwhen receptors for signaling molecules are membrane proteins the transduction stage is multistep pathwayusually involves inactive/active state by adding/removing phosphate groupbenefit of multistep pathway is that possibility of amplification of signalif each step on pathway can transmit signal to several molecules end up with large # activated molecules @ end of pathwaySignal Transduction Pathwayin most cases original signaling molecule does not enter cell & is not passed along signaling pathway1st step triggered by signaling molecule binding to receptorproteins often used as relay molecules (protein interaction a unifying theme of all cellular regulation)Protein Phosphorylation & Dephosphorylationprotein kinase: enzyme that transfers phosphate groups from ATP proteinmost act on proteins different than themselvesmost act on a.a. serine or threonine (not tyrosine as in previous example)includes kinases in plants, animals, & fungimany relay molecules in pathway are kinasesPhosphorylation Cascade

Protein Phosphatasesenzymes 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

Second Messengersmany signaling pathways involve small, nonprotein, water-soluble molecules or ions known as 2nd messengers1st messenger is extracellular signaling molecule2 most widely used 2nd messengers are cAMP & Ca++Cyclic AMPepinephrine causes glycogen in hepatocytes to glucose w/out entering cellssearch for 2nd messenger that transmits signal from plasma membrane metabolic pathway in cytoplasmepinephrine binding to receptor followed by elevation of cytosolic concentrations of cAMPcAMP


Adenylyl Cyclaseenzyme embedded in plasma membraneATP 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


cAMP as 2nd Messenger1st messenger activates G protein-coup-led receptor adenylyl cyclase ATP to cAMP activates another protein (usually protein kinase A)

Protein Kinase Aserine/threonine kinaseonce activated it will phosphorylate other proteins (depends on cell type)

Other Regulation MechanismsG protein systems inhibit adenylyl cyclaseuses different signaling molecule & receptor

understanding role of cAMP helps to explain how certain microbes cause diseaseVibrio cholerae: causes cholerain contaminated waterforms biofilm over small intestinesproduces 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)Vibrio cholerae

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

Animal CellsPlant Cellscontractionsecretion cell division

pathway that leads to greening in response to lightEffects of Ca++

Ca++ Concentration Gradientnormally, [Ca++] inside cell 1 site (not just either on or off)4 aspects of fine-tuning response:Signal amplificationSpecificityEfficiencyTermination of signalSignal Amplificationenzyme cascades amplify the cells response to a signal@ each step the # of activated products much > in preceding step of cascadeamplification happens because activated protein kinase stays in activated form long enuf to process numerous molecules of substrateas result a small # signal molecules (like epinephrine) can release 100s of millions of final product (glucose molecules)

Specificity of Cell Signaling & Coordination of the Responsecertain cells respond to some signals & have no response to others 2 different cells may have different responses to same signaldifferent kinds of cells turn on different genes so different kinds of cells have different collections of proteinsWhat controls responses in cells?response of a particular cell to a signal depends on its particular collection o signal receptor proteinsrelay proteinsproteins necessary to carry out the response

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 transductio