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1 CellCommunicationRecap 1CellCommunication • • • • • • • • • Listthetypesofsignalsinvolvedincommunicationandwheretheycome from. Describethetypesofsignaltransductionpathwaysthatareunderstrong selectivepressure. Explainhowbacteriacanusequorumsensingasanexampleofhowsignal transductionpathwaysinfluencehowthecellrespondstoitsenvironment. UsingEpinephrinestimulationofglycogenbreakdowninmammals,explain howinmulticellularorganisms,signaltransductionpathwayscoordinatethe activitieswithinindividualcellsthatsupportthefunctionoftheorganismasa whole. Usingplasmodesmataasanexampleexplainhowcellscommunicatebycellto-cellcontact. Usingneurotransmitters,explainhowcellscommunicateovershortdistances byusinglocalregulatorsthattargetcellsinthevicinityoftheemittingcell. Explainhowsignalsreleasedbyonecelltypecantravellongdistancesto targetcellsofanothercelltype. Describehowdifferentmessengersbindtodifferentsignalsandexplainhow areceptorproteinisactivatedtotransducethesignal. Describetheprocessofsignaltransductionandexplaintheroleofsecond messengers. TypesofCellSignaling • Directcontact:cellscanreceiveinformationwhentheirmembranecontacts anothercell'smembranethroughcell-cellrecognition.Thistypeofsignaling caninvolvereceptorsrecognizingcellsorinvolvecelljunctions(like plasmodesmata)connectingcellstoeachother.Importantforembryonic developmentandimmuneresponse. • Paracrinesignaling:shortrangeandshort-livedsignalingwherecellssecrete signalstonearbyneighbors.Acommonexamplewouldbeagrowthfactor. Cellscansecretegrowthfactorstoencouragenearbyneighborstogrow. o Synapticsignaling:specializednervoussystemsignaling.Shortranged, butveryfast.Electricalsignalstriggerthereleaseofneurotransmitters whichpassthemessagetoatargetcell. • Autocrinesignaling:signalingwherethecellsendsthesignaltoitself. Prevalentinapoptosissignaling,development/differentiation,and inflammatoryresponse • Shortrange/localplantsignalingislessunderstoodastheyusedifferent mechanismsthananimals. 2 • Hormonesignaling:hormonesaresecretedfordistributionacrosslong distances.Inanimals,thismeanstheuseofthecirculatorysystem.Inplants, thiscanmeanthroughvesselsorthroughgas.Hormonesignalingisgenerally farreaching,longlasting,andslowerthanlocalsignaling.Importantto distinguishthathormonesareusedforlongdistancesignaling.Endocrinecells cansecretehormonesthattravelthroughthecirculatorysystembefore arrivingatatargetcellontheotherside. DirectContact-Plasmodesmatasignaling • Plasmodesmataallowthedirectpassageofmoleculesbetweencells.Soifone plantproducesasignaltostimulategrowth,anycelldirectlyconnectedtoit throughplasmodesmatamayalsoreceivethesamesignalandproducea similarresponse.Thus,aplantcellmaycommunicatetoitsneighborswhenit isappropriatetogrowbysharingitsgrowthfactors,thuscoordinatinga growthresponsethroughoutmanycells. QuorumSensing-sensingandrespondingtolocalpopulationdensity • Thisprocessisexemplifiedinbacteria. • Quorumsensingcanbedescribedasdensitydependentresponses.Inthe lecture,anexampleisprovidedusingautoinducers. o Whencellsareinlowdensity,theseautoinducersdiffuseoutofthecell andsothecellsdonotproducemuchautoinducers.Thisresultsinlow concentrationsofautoinducerssolongaspopulationdensityislow. o Whencellsareinhighdensity,theautoinducersstayinthecelland causethecelltoproducemoreautoinducers.Thisresultsinapositive feedbackloop,resultingincontinuallyhighconcentrationsof autoinducerssolongaspopulationdensityishigh. o Bycouplingtheseautoinducerswiththeexpressionofgenes,bacteria canuseautoinducerstoinactdensitydependentresponses.Thisalso meansthatsinglecelledorganismscancoordinateresponsesas groups.Autoinducedresponseswillresultinanentirepopulation respondingsimilarly. • Sinceautoinducersareancientintermsofevolution,itishypothesizedthat autoinducers(andquorumsensingingeneral)maybeevolutionarily significant.Theabilitytocoordinateresponsesbetweenmultiplecellsthrough localsignalswouldhavebeenimportantforearlymulticellularorganisms. SelectivePressuresonSignalTransductionPathways • Aquicknote;Itrytobeconciseinthesesummariesbutforthispoint,Iwould liketosharetheentireexplanationthatwasprovidedtomebyoneofmy teachers. • Naturalselectiondrivesevolutiontowardswhicheverversionofanorganism thatcanbestreproduceandpropagatemoreversionsofitself.When 3 resourcesarescarce,thismaymeannaturalselectiondrivesevolution towardsefficiency.Cellcommunicationmayhavebeenselectedsinceitallows cellstoreacttotheenvironmentandthusbemoreefficient,gatheringfood whenitismostplentifulandconservingenergyduringtimeswhenitwouldbe wastefultoexpendit.Thus,weseethattheideaofcellsignalingwouldbe favorablebutwhydoweseelongseriesofsignalsintheformofsignal transductionpathwaysinsteadofanefficient,short,singlesignalfrom stimulustoresponse?Signaltransductionpathwaysallowforasignaltobe propagated/amplified.Amultistepprocesscanallowmultiplesignalstolead tothesameresponse,orasinglesignaltoleadtomultipleresponses.Thus,an “inefficient”routeforasingletaskmaybemoreefficientwhenyouconsider theflexibilitythatamulti-stepprocessprovides.Naturalselectionmay therefore,haveselectedforacompromisebetweenefficiencyandflexibility. SignalTransductionPathway-aseriesofsignalsthatleadstoacellularresponse • ProteinPhosphorylationandDephosphorylation o Ineachstepofapathway,areceptor'sshapeischangedinorderto triggerthenextstep.Thischangeinshapeoftencomesintheformof phosphorylation. o KinaseisresponsiblefortakingaphosphatefromATPandaddingitto amolecule.Verycommoninsignalpathways. o Phosphataseisresponsiblefortakingaphosphatefromamolecule. Usedtoresetpathways. o ThinkofPhosphorylation/DephosphorylationasanOn/Offswitch.For manymolecules,havinganattachedphosphategroupturnstoprotein intothe“on”positionandacertainspecificactivitybegins.Toturnoff thisactivity,theproteinmustbedephosphorylated.(Insomeproteins, it'sreversed). • SecondMessengers-smallmoleculesandionsthatrelaymessages o Gproteincoupledreceptor § Areceptorisresponsibleforreceivingandbindingtoasignal. ThisreceptorthenactivatesaGproteinthereceptoriscoupled with.Gproteincoupledreceptorsareresponsibleforactivating Adenylylcyclase. o CyclicAMP § AdenylylcyclaseconvertsATPtocAMP. § WhenasignalactivatesAdenylylcyclase,thesignalispassedon whenATPisconvertedtocAMP.cAMPisthenpassedontoa kinasewhichisactivatedbycAMP. • EpinephrineasanExample o Epinephrineisahormonealsoknownasadrenaline. StartwithasingleEpinephrine (1epinephrine) 1.EpinephrinebindstoaGprotein (102activatedGproteins) coupledreceptor. 4 2.Gproteincoupledreceptor activatesadenylylcyclase. 3.AdenylylcyclaseconvertsATP tocAMP. 4.cAMPactivatesproteinkinase A. 5.ProteinKinaseA phosphorylatesphosphorylase kinase. 6.PhosphorylaseKinase phosphorylatesglycogen phosphorylase. 7.Glycogenphosphorylasefinally performsthecellularresponse.It convertsglycogentoglucose-1phosphate. (102adenylylcyclases) (104cyclicAMP) (104proteinkinaseAs) (105phosphorylasekinases) (106glycogenphosphorylases) (108Glucose-1-phosphates) o Asthepathwayproceeds,thesignalisamplified.Asingleepinephrine activates102Gproteins.102adenylylcyclaseswillcreate104cyclic AMPs.etc.Thus,weseehowasingleepinephrinecanamplifyasignal toproduce108glucose-1-phosphatessincemanyproteinsinthe responsecanperformataskmorethanoncebeforeitisinactivated. o Theimportanttakeawayfromthisisthatbyusingmultiplesteps,acell canregulateareactioninwayssuchasamplifyingaspecificresponse. Synapticsignaling • Avoltagegoingthroughaneuroncausesavoltagegatedchanneltoopen, allowingCalciumionstorushintothecell.TheCalciumionscausethecellto releaseneurotransmitters.Theneurotransmitterstraveltowardsits neighboringcell,ontheothersideofthesynapse.Here,theneurotransmitter bindstoaligandgatedionchannel.Theionchannelopens,allowingionsto flowinandout.Thisligandgatedionchannelthuscausesavoltagetobesent throughthereceivingneuron.Theneurotransmitterisquicklyreleasedand thesignalstopsastheneurotransmitterisremovedanddegraded. Areminder! • Asthisisalloccurring,recallthatalloftheseproteinsworkbychanging shapes.Structure=function! 2TheCellCycle • Explainthereasonsforcelldivisionandwhycellsmaynotdivideafter maturity,giveexamples. 5 • • • • • • • • • • • Describethephasesofthecellcycleandwhathappenstothechromosomes ineachphase. ExplainhowDNAcanfitinthenucleusofthecellwithchromosomefolding; describethedifferencesbetweenchromatinandchromosomes. Describethestructureofametaphasechromosome. Compareandcontrasttheprocessesoftelophaseandcytokinesis. Explainthedifferencesbetweenplantandanimalcellseparation. Describehowbacteriadivideandhowthisprocessisdifferentfrommitosis. Describethefactorsthatmustbepresentforthecelltodivide. DescribethecheckpointsofthecellcycleandwhyacellwouldbeplacedinG0 phase. Describetheroleofcyclinsincellcycleregulation. Explaintheroleoftumorsuppressorgenes/proto-oncogenesandhowthey canleadtocancer. Explaintheevolutionarylinkbetweenbinaryfission,mitosis,anddivisionof variousprotists. Celldivision:Whybother? • Forsinglecelledorganisms,celldivisionistheirmeansofreproductionand propagatingtheirgenes.Cellsthatreproducearetheoneswhosegenes survive! • Formulticellularorganisms,celldivisionallowstheorganismtogetbigger. Largersizecanmeanbeingabletosurvive(bybeingabletoobtainmorefood orwardoffpredators),reachingreproductivematurity,etc. • Cellsmaystopdividingaftermaturity,especiallyinmulticellularorganisms.In multicellularorganisms,cellsdifferentiateintospecifictypesofcells.This differentiationallowsthemtoperformspecifictasksandsomeofthesecell typesnolongerneedtodivide.Forexample,theneuronsinyourbrain! DNApackaging • DNAwouldbeverylongifyoustretcheditallthewayout.Inordertofitinside thenucleusofacell,itmustbefoldedup.We'reallfamiliarwiththeDNA doublehelix.ThenextsteptoDNAstructureiswrappingthehelixarounda histone.TheDNAatthispointisthenwrappedaroundtoformnucleosomes. BycoilingtheDNA,youcancondenseitandmakeittakeupmuchlessspace. EukaryoticCellCycleSummary • Interphase o G1phase-gapphase;grows o Sphase-synthesis;geneticmaterialisduplicated o G2phase-gapphase;getsreadyfordivision o Interphasetakesupmostofacell'slife • MPhase 6 • o Mitosis § Prophase • Chromatincondensesintodiscretechromosomes.These chromosomesaresisterchromatidsjoinedtogetherat centromeres. • Mitoticspindlebeginstoform. • Centrosomesmoveawayfromeachother. § Prometaphase • Nuclearenvelopefragments. • Microtubulesextendintonucleararea. • Chromosomescontinuetocondense.Chromatidsnow haveakinetochorewhichattachtosomemicrotubules. § Metaphase • Centrosomesnowatoppositeends. • Chromosomesalignalongthemetaphaseplate(an imaginarylinebetweenthecentrosomes) § Anaphase • Cohesionproteinsarecleavedsothatsisterchromatids cansuddenlypartways.Eachchromatidbecomesa chromosome. • Thechromosomesmovetowardsoppositeends,thecell elongates. • Attheendofanaphase,eachofthetwoendsofthecell haveequalhalvesofthechromosomes § Telophase • Twodaughternucleiform,oneineachhalf • Chromosomesloosenup § Cytokinesis • Overlapswithtelophase;thecytoplasmissplitand dividedintotwoparts.Thebeginningofthisprocessis markedbyacleavagefurrow,whichpinchesthecellinto twohalves.Thecleavagefurrowisformedbya contractileringofmicrofilaments. Plantcellsmustformacellwallduringcelldivision;thiscellwallissufficientto dividethecytoplasmandsocleavageasitoccursinanimalcellsdoesn'treally occur.Instead,acellplateformsduringmitosiswhichextendsintoafullcell wall. ProkaryotesgothroughBinaryFission • Recallthatbacteriadonothavenucleiandthattheirgeneticmaterialconsists ofasinglecircularstrand.Thus,theirreplicationprocessisdifferent. o 1.Chromosomereplication. 7 • o 2.Asreplicationcontinues,theoriginsofreplication(ofwhichthere arenowtwocopies)movestooppositeendsofthecell.Thecell elongates. o 3.Theplasmamembranegrowsinwardandanewwallformsto separatethetwosides. o 4.Twodaughtercellsresult. Someprotiststhatgothroughbinaryfissiondemonstrateabasicspindle formation.Thissuggestsanevolutionarylinkbetweenmitosisandbinary fission,withthisprotistformafissionservingasanintermediate. Cellularcontrolsystem • Cellshavecheckpointsalongtheircellcyclethatmustbepassedbeforethe nextstagemaybegin.ThereistheG1checkpoint,theG2checkpoint,andthe Mcheckpoint.IfacelldoesnotpasstheG1checkpoint,itentersaG0phase wherethecellnolongerdivides.MosthumancellsareinG0phase. • CyclinandCyclindependentKinases(cdk) o Theproteinsneededforthecellcyclegenerallystayatthesame concentrationthroughout,buttheiractivationchangesdependingon thefluctuatingconcentrationofcyclins,whichactivatecdks. o Example: § 1.CyclinproductionstartsinSphaseandcontinuesthroughG2 phaseuninterrupted. § 2.Cyclinaccumulatesuntilitreachesahighenough concentrationthatitbindswithCDKs.WhenenoughCyclin-CDK complexesform,thecellcanproceedthroughtheG2 checkpointtothenextphase. § 3.ThisCyclin-CDKcomplex,we'llcallMPFormaturation promotingfactor...MPFphosphorylatesproteinsinorderto promotemetaphase. § 4.Attheendofmitosis,MPFissplit.CDKbecomesinactive whilecyclinisdegraded. § 5.Wereturntothebeginning,withnocyclinuntilitstartsto buildupagain. o Eachcheckpointisregulatedinasimilarmannerwithcyclins! Cancer • Cancerisessentiallyamassofcellsthatnolongerdivideproperly.Ithasa largevarietyofcausesandforms. • Proto-oncogene-genesthatcodeforregulatoryproteinsinvolvedinprotein growthandcelldivision • Tumorsuppressinggenes-genesthatcodeforproteinsthatinhibitcell division 8 • Canyouseehowmalfunctioningversionsofthesegenescouldleadtocancer? Ifproteinsdonotinhibitcelldivision,thencellsdivideoutofcontrol.If improperregulationoccurs,