Cell MigrationAn Overview.docx
- 文档编号:23299120
- 上传时间:2023-05-16
- 格式:DOCX
- 页数:11
- 大小:22.29KB
Cell MigrationAn Overview.docx
《Cell MigrationAn Overview.docx》由会员分享,可在线阅读,更多相关《Cell MigrationAn Overview.docx(11页珍藏版)》请在冰豆网上搜索。
CellMigrationAnOverview
CellMigration——AnOverview
vol.294GuanJ.-L.(ed.)CellMigration-DevelopmentalMethodsandProtocolsChapter1
Summary
Cellmigrationisanessentialprocessfornormaldevelopmentandhomeostasisthatcanalsocontributetoimportantpathologies.Notsurprisingly,thereisconsiderableinterestinunderstandingmigrationonamolecularlevel,butthisisadifficulttask.However,technologiesarerapidlyemergingtoaddressthemajorintellectualchallengesassociatedwithmigration.Inthischapter,weoutlinethebasicsofcellmigrationwithanemphasisonthediversesystems,methodologies,andtechniquesdescribedinthisbook.
Fromthecontributionspresented,itisapparentthatthenextfewyearsshouldproducemajoradvancesinourunderstandingofcellmigration.
KeyWords:
Cellmigration;adhesion;signaling;protrusion;development.
1.Introduction
Cellmigrationisacomplexprocessthatisessentialforembryonicdevelopmentandhomeostasis(1,2).Ingastrulation,migrationisparticularlyrobust,whereessentiallyallcellsmigrateassheetstoformthethreelayers,includingendoderm,ectoderm,andmesodermthatcomprisetheresultingembryo.Cellswithintheselayersmigratetotargetlocationsthroughoutthedevelopingembryo,wheretheydifferentiateandformvarioustissuesandorgans.Themigrationofcellsfromepitheliallayerstotheirtargetsisageneralphenomenonthatoccursthroughoutdevelopment.Inthedevelopingcerebellum,neuronalprecursorcellsmigratefromtheepitheliumtotheirresidencesindistinctlayers.Onespecialformofmigrationduringdevelopmentistheextensionofneurites.Thetipofadevelopingneurite,thegrowthcone,sharesmanysimilaritieswithamigratingcell.Thepreciseguidanceandtargetrecognitionofgrowthconesarecentraltotheestablishmentoftheneuronalnetworkandthuscognitivefunctions.
Migrationisnotlimitedtodevelopment,butoccursintheadult,whereitiscentraltobothnormalandpathologicalstates.Forexample,themigrationofprecursorcellsfromthebasallayertotheepidermisfunctionstocontinuouslyrenewskin.Otherhomeostaticprocesses,includingwoundrepairandmountinganeffectiveimmuneresponse,alsorequiremigration.Leukocytemigrationfromthecirculationintothesurroundingtissue,wheretheyingestbacteria,isimportantformountinganimmuneresponse.Migrationalsocancontributetosomepathologicalprocesses,suchasvasculardisease,chronicinflammatorydiseases,andtumorformationandmetastasis.Forexample,tumorformationisaccompaniedbytheconstructionofanewvascularnetwork,whichinvolvesmigrationoftheendothelialcellsfrompre-existingbloodvesselsintothetumor,wheretheyproliferateandformthenewvessels(angiogenesis).
Migrationalsooccursduringmetastasiswhensometumorcellsmigrateoutoftheinitialtumorintothecirculationandmovetonewlocations,wheretheyformasecondarytumor.Becausetheinvasionoftumorcellsfromtheprimarysiteintothesurroundingareaandangiogenesisisessentialfortumordevelopment,assayshavebeendevelopedtostudytheseprocesses.InChapter9,ShawoutlinesanassayforexaminingtheinvasionoftumorcellsthroughMatrigel.AssaystodissectthesignalingeventsinvolvedinendothelialcellmigrationandmodelsystemsforangiogenesisaredescribedinChapters10,11,and19.
Althoughmanystudieshaveexaminedcellmigrationinvertebrates,migrationisequallyimportantininvertebrates,plants,andsomesingle-cellorganisms.
Forexample,duringdevelopmentofCaenorhabditiselegans,cellsmigratewithintheembryoalongdefinedtrajectories.Eachcellstopstodivide,andthedaughtercellscontinuetomigrate.BecauseofthesmallsizeandthetransparencyofC.elegans,individualcellscanbefollowedastheymigrateinlivingembryos,makingitasimplesystemforstudyingmigration.InChapter13,ShakirandLundquistdescribethemethodsforanalyzingmigrationinC.elegans.Anotherinvertebratemodelsystemisthefruitfly,Drosophilamelanogaster.Drosophilahasamorecomplicatedbodyplanandthereforehasincreasedcomplexityinitsmigrationpatternsduringdevelopmentandadultlife.Oneexampleisprimordialgermcells,whichmigratethroughthemidgutepitheliumandattachtothemesoderm,wheretheyassociatewiththegonadalprecursorsandeventuallyformagonadoneithersideoftheembryo.Chapters14and15outlineprotocolsforstudyingmigrationofdifferentcelltypesinDrosophilaandliveimagingofDrosophilaembryos.Theinformationgainedfromstudyinginvertebratecellmigrationcanbeveryusefulforunderstandingmigrationinmorecomplexorganisms,asconfirmedbythehighdegreeofhomologybetweenmanyinvertebrateandvertebrategeneproductsthatareinvolvedinmigration.
2.TheMigratoryCycle
Migrationcanbethoughtofasacyclicalprocess.Itbeginswhenacellrespondstoanexternalsignalbypolarizingandextendingaprotrusioninthedirectionofmovement.Theformationofadhesioncomplexesfunctionstostabilizetheprotrusionbyattachingittothesubstratumonwhichthecellismigrating.Theseadhesions,whichserveastractionpointsformigration,initiatesignalsthatregulateadhesiondynamicsandprotrusionformation(3).
Contractionthenmovesthecellbodyforwardandreleaseoftheattachmentsattherear,asthecellretracts,completesthecycle.Slow-movingcells,suchasfibroblasts,showthesedistinctstepsofmigration,buttheyarelessobviousinothercelltypes.Forexample,rapidlymigratingcells,suchaskeratocytesandleukocytes,glideoverthesubstratumbyprotrudingandretractingsmoothlywithoutformingobviousattachments.
2.1.Polarization
Manydifferentmoleculesserveasexternalagentsthatinitiateandpromotemigration.Forexample,somemoleculesinitiateamigratoryphenotype(chemokinetic)whereasothersresideinsoluble(chemotactic)-orsubstrate(haptotactic)-associatedgradientsandleadtodirectedmovement.Thesemoleculesandtheirreceptorsarewellstudiedinleukocytes.Thesecellscansensethepresenceofevenashallowgradient,inwhichtheypolarizeandmigratepersistentlyinonedirection(4).Theirpersistentpolarityisapparentwhenthecellssensechangingchemotacticgradientsandtheentirecellturnsratherthanextendinganewprotrusionfromanotherregion.Incontrast,fibroblastsaremoreplasticandcanextendprotrusionsfromanypositioninthecellastheychangedirections.AnalysisofdirectionalcellmigrationusingtheBoydenchamberandtheDunnchemotaxischamberarediscussedinChapters2and4.Inaddition,Chapter24outlinesamethodforgeneratinggradientsforstudyingdirectionalcellmigration.
2.2.AdhesionComplexes
Adhesioncomplexes,whicharesitesofattachmentbetweenthecellandtheextracellularmatrix(ECM),arecomposedofanumberofproteins,includingtheintegrinfamilyoftransmembranereceptors,kinases,adaptorandstructuralmolecules(3).IntegrinsserveasthefunctionalconnectionbetweentheECMandtheactincytoskeleton.ThesmallGTPase,Rac,inducestheformationofsmalladhesionsattheleadingedge(5–7).Theseadhesionsserveastractionpointsandtransmitstrongpropulsiveforcesthatmovethecellbodyforward(8).Thematurationofthesesmalladhesionsintolarger,moreorganizedstructuresactuallyinhibitsmigration(3,9).InChapter5,KucikandWupresentprotocolsforanalyzingcelladhesionunderstaticconditionsandshearstress,andinChapter6,BerrierandLaFlammeprovideamethodtoquantifycellspreading,whichisanimportantaspectofcelladhesion.Finally,inChapter21,Dreesetal.describemethodsforanalyzingproteincomplexesatthecellmembraneaftercell–cellandcell–ECMadhesion.
Becausetyrosinephosphorylationofadhesioncomponentsisthoughttoregulatetheirdynamics,thereisgreatinterestinstudyingthisprocess.Thiscanbeaccomplishedwitha“phosphotyrosinereporter”inwhichyellowfluorescentprotein(YFP)isfusedtotwophosphotyrosine-bindingSrc-homology2-domainsderivedfromc-Src(10).Quantitativefluorescentmicroscopywiththisreporterhasbeenusedtostudythekineticsoftyrosinephosphorylationinadhesions.DetailsofthismethodareprovidedinChapter20.
2.3.MovingForwardandTrailingBehind
Actin–myosincontractilityatthefrontofthecellservestopullthecellbodyforwardinthedirectionofmovement.Releaseofadhesionsatthecellrearandretractionofthetailarealsomediatedbymyosin.SpatialandtemporalregulationofRhoGTPasescontrolstheseprocessesthrougheffectors,suchasRhokinase,thatregulateactomyosincontractility.RhokinasehasbeenimplicatedinreleaseofadhesionsatthecellrearthroughregulationofmyosinII(11).
Othermoleculesimplicatedinthereleaseofadhesionsincludetheproteasecalpainandaphosphatase,calcineurin(12,13).Microtubulesalsofunctionintheregulationofadhesiondisassembly,probablythroughthemodulationofRacactivity(14).
3.ModesofMigration
3.1.Single-CellMigration
Asdiscussedpreviously,themigrationofindividualcellsrequirestheasymmetricalorganizationofcellularactivities.Inculture,manydifferentcelltypescanbecomepolarizedwithafrontandrearasymmetry,butthisisusuallytransientandresultsinrandommigration.Thestabilized,directionalmovementofcellsrequiresexternalcues.Intissue,theseexternalcuesaretypicallyprovidedbythesurroundingenvironment.Theexternalcuesactivateintracellularsignalingpathwaysthatcontrolpolarizationanddirectedcellmovement.ThesmallGTPases,Rac,andCdc42,playaprominentroleinregulatingthisprocess(5,6).
3.2.MonolayerCellMigration
Duringembryogenesis,manycellsdonotmigrateassinglecellsbutratherassheetsorlooselyassociatedclusters.Invitro,scratchingorwoundingacellmonolayerinducesthesynchronizedm
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- Cell MigrationAn Overview
![提示](https://static.bdocx.com/images/bang_tan.gif)