Format

Send to

Choose Destination
Nat Neurosci. 2009 Jul;12(7):848-56. doi: 10.1038/nn.2322. Epub 2009 May 31.

Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.

Abstract

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.

PMID:
19483689
PMCID:
PMC2714269
DOI:
10.1038/nn.2322
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center