THE JOURNAL OF CELL BIOLOGY E The online version of this article containssupplementalmaterial. Theonlineversionofthisarticle total internal refl total internal SA,streptavidin;Tf,transferrin;TfR,Tfreceptor;TIRF,domain; PE,phycoerythrin; NMJ, neuromuscularjunction;Pak,p21-associated kinase;PBD,Pak-binding glycosyl-phosphatidylinositol; LAMP, lysosomal-associatedmembraneprotein; system;EEA1,earlyendosomalantigen1;GPI, receptor; CNS,centralnervous Abbreviationsusedinthispaper: MedicalSchool,Boston,MA02115. Boston, Harvard R.Massol Madison, WI53706.
B.Chanda School ofMedicine,Seattle,WA 98195. © A.Chaudhry CorrespondencetoSatyajitMayor:[email protected] S.KumariandV. Borronicontributedequallytothispaper. and thisprocessmaycontribute tosynapticplasticity ( Tehrani shown tooperateinvarious structurallyrelatedionchannels, sponse toexternal signals. Agonist-induced endocytosis hasbeen distrib nance ofreceptorsatspecifi Communication atsynapsesrequiresthelocationandmainte- Introduction accessibilityoffl surface indicated bydifferential uores- row, tubular, whichare compartments, surface-connected occurs viasequestrationofAChR cells orendogenouslyinC2C12myocytes.Internalization when expressedheterologouslyinChinesehamsterovary AChRtolateendosomes ofcellsurface the internalization toxin ( show thatbindingofthecompetitiveantagonist system.Wepathology ofsynapsesinthecentralnervous 3 2 1 and Sudha endocytic pathway via aRac-dependent,dynamin-independent Nicotinicacetylcholinereceptorisinternalized www.jcb.org/cgi/doi/10.1083/jcb.200709086 1179–1193 J. CellBiol.Vol. 181No.7 $30.00 The RockefellerUniversity Press and MolecularNeurobiology, BahiaBlancaB8000FWB,Argentina NationalInstituteofImmunology, NewDelhi110067,India InstitutodeInvestigacionesBioqu NationalCentreforBiologicalSciences,Tata InstituteofFundamentalResearch,Bangalore560065,India 2008 Francisco J. Kumarietal. modulation atneuromuscularjunctionsandinthe (AChR) isaproposedmajormechanismofneuro- ndocytosis ofthenicotinicacetylcholinereceptor ution ofreceptorsarecriticaldeterminantsthecellre-