Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking.
Postsynaptic receptor localization is crucial for synapse development and function, but the underlying cytoskeletal mechanisms remain elusive. Using Xenopus neuromuscular junctions as a model, we found that actin depolymerizing factor (ADF)/cofilin regulated actin-dependent vesicular trafficking of acetylcholine receptors (AChRs) to the postsynaptic membrane. Active ADF/cofilin was concentrated in small puncta adjacent to AChR clusters and was spatiotemporally correlated with the formation and maintenance of surface AChR clusters. Notably, increased actin dynamics, vesicular markers and intracellular AChRs were all enriched at the sites of ADF/cofilin localization. Furthermore, a substantial amount of new AChRs was detected at these ADF/cofilin-enriched sites. Manipulation of either ADF/cofilin activity through its serine-3 phosphorylation or ADF/cofilin localization via 14-3-3 proteins markedly attenuated AChR insertion and clustering. These results suggest that spatiotemporally restricted ADF/cofilin-mediated actin dynamics regulate AChR trafficking during the development of neuromuscular synapses.
Lee
Chi Wai
CW
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Han
Jianzhong
J
Bamburg
James R
JR
Han
Liang
L
Lynn
Rachel
R
Zheng
James Q
JQ
D048948:14-3-3 Proteins / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D018171:Agrin / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D051345:Destrin / Q000378:metabolism*; D032342:Muscle Cells / Q000378:metabolism; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013997:Time Factors; D022161:Transport Vesicles / Q000378:metabolism*; D014981:Xenopus
D048948:14-3-3 Proteins; D051339:Actin Depolymerizing Factors; D000199:Actins; D018171:Agrin; D051345:Destrin; D011950:Receptors, Cholinergic