Mammaliancellmotilityrequiresactinpolymerizationinthedirectionofmovementtochangemembraneshapeandextendcytoplasmintolamellipodia.Thepolymerizationofactintodrivecellmovementalsoinvolvesbranchingofactinfilamentsintoanetworkorientedwiththegrowingendsofthefibersnearthecellmembrane.ManipulationofthisprocesshelpsbacterialikeSalmonellagainentryintocellstheyinfect.TwooftheproteinsinvolvedintheformationofYbranchesandincellmotilityareArp2andArp3,bothmembersofalargemultiproteincomplexcontainingseveralotherpolypeptidesaswell.TheArp2/3complexislocalizedattheYbranchjunctionandinducesactinpolymerization.Activityofthiscomplexisregulatedbymultipledifferentcellsurfacereceptorsignalingsystems,activatingWASP,andArp2/3inturntocausechangesincellshapeandcellmotility.WaspanditscousinWave-1interactwiththeArp2/3complexthroughthep21componentofthecomplex.ThecrystalstructureoftheArp2/3complexhasrevealedfurtherinsightsintothenatureofhowthecomplexworks.ActivationbyWave-1,anothermemberoftheWASPfamily,alsoinducesactinalterationsinresponsetoRac1signalsupstream.Wave-1isheldinaninactivecomplexinthecytosolthatisactivatedtoallowWave-1toassociatewithArp2/3.WhileWASPisactivatedbyinteractionwithCdc42,Wave-1,isactivatedbyinteractionwithRac1andNck.Wave-1activationbyRac1andNckreleasesWave-1withHspc300toactivateactinYbranchingandpolymerizationbyArp2/3.Differentmembersofthisgenefamilymayproducedifferentactincytoskeletalarchitectures.TheimmunologicaldefectsassociatedwithmutationoftheWASPgene,theWiskott-AldrichsyndromeforwhichWASPwasnamed,indicatestheimportanceofthissystemfornormalcellularfunction.

Contributor:KosiGramatikoff,PhD

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