Download Cell communication recup

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CellCommunicationRecap
1CellCommunication
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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.
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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
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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.
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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
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Explainthereasonsforcelldivisionandwhycellsmaynotdivideafter
maturity,giveexamples.
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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
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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.
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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
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Canyouseehowmalfunctioningversionsofthesegenescouldleadtocancer?
Ifproteinsdonotinhibitcelldivision,thencellsdivideoutofcontrol.If
improperregulationoccurs,