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

Chi Wai Lee; Jianzhong Han; James R. Bamburg; Liang Han; Rachel Lynn; James Q. Zheng

doi:10.1038/nn.2322

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

Chi Wai Lee, Jianzhong Han, James R. Bamburg, Liang Han, Rachel Lynn, James Q. Zheng

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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.

Original language	English (US)
Pages (from-to)	848-856
Number of pages	9
Journal	Nature neuroscience
Volume	12
Issue number	7
DOIs	https://doi.org/10.1038/nn.2322
State	Published - Jul 2009
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1038/nn.2322

Cite this

@article{fc698b2089f04695bd3aa5235f18bea2,

title = "Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking",

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.",

author = "Lee, {Chi Wai} and Jianzhong Han and Bamburg, {James R.} and Liang Han and Rachel Lynn and Zheng, {James Q.}",

note = "Funding Information: We would like to thank B. Lu (National Institute of Child Health and Human Development) for his help in our electrophysiological experiments. This work is supported by grants from National Institutes of Health to J.Q.Z. (GM083889 and AG029596) and J.R.B. (NS40371). C.W.L. was supported by a postdoctoral fellowship from The Croucher Foundation.",

year = "2009",

month = jul,

doi = "10.1038/nn.2322",

language = "English (US)",

volume = "12",

pages = "848--856",

journal = "Nature neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "7",

}

TY - JOUR

T1 - Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking

AU - Lee, Chi Wai

AU - Han, Jianzhong

AU - Bamburg, James R.

AU - Han, Liang

AU - Lynn, Rachel

AU - Zheng, James Q.

N1 - Funding Information: We would like to thank B. Lu (National Institute of Child Health and Human Development) for his help in our electrophysiological experiments. This work is supported by grants from National Institutes of Health to J.Q.Z. (GM083889 and AG029596) and J.R.B. (NS40371). C.W.L. was supported by a postdoctoral fellowship from The Croucher Foundation.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67649822159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649822159&partnerID=8YFLogxK

U2 - 10.1038/nn.2322

DO - 10.1038/nn.2322

M3 - Article

C2 - 19483689

AN - SCOPUS:67649822159

SN - 1097-6256

VL - 12

SP - 848

EP - 856

JO - Nature neuroscience

JF - Nature neuroscience

IS - 7

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this