HSP90β Regulates Rapsyn Turnover and Subsequent AChR Cluster Formation and Maintenance

Shiwen Luo, Bin Zhang, Xian ping Dong, Yanmei Tao, Annie Ting, Zheng Zhou, James Meixiong, Junjie Luo, F. C.Alex Chiu, Wen C. Xiong, Lin Mei

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Rapsyn, an acetylcholine receptor (AChR)-interacting protein, is essential for synapse formation at the neuromuscular junction (NMJ). Like many synaptic proteins, rapsyn turns over rapidly at synapses. However, little is known about molecular mechanisms that govern rapsyn stability. Using a differential mass-spectrometry approach, we identified heat-shock protein 90β (HSP90β) as a component in surface AChR clusters. The HSP90β-AChR interaction required rapsyn and was stimulated by agrin. Inhibition of HSP90β activity or expression, or disruption of its interaction with rapsyn attenuated agrin-induced formation of AChR clusters in vitro and impaired the development and maintenance of the NMJ in vivo. Finally, we showed that HSP90β was necessary for rapsyn stabilization and regulated its proteasome-dependent degradation. Together, these results indicate a role of HSP90β in NMJ development by regulating rapsyn turnover and subsequent AChR cluster formation and maintenance.

Original languageEnglish (US)
Pages (from-to)97-110
Number of pages14
JournalNeuron
Volume60
Issue number1
DOIs
StatePublished - Oct 9 2008

Keywords

  • DEVBIO
  • MOLNEURO
  • PROTEINS

ASJC Scopus subject areas

  • Neuroscience(all)

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    Luo, S., Zhang, B., Dong, X. P., Tao, Y., Ting, A., Zhou, Z., Meixiong, J., Luo, J., Chiu, F. C. A., Xiong, W. C., & Mei, L. (2008). HSP90β Regulates Rapsyn Turnover and Subsequent AChR Cluster Formation and Maintenance. Neuron, 60(1), 97-110. https://doi.org/10.1016/j.neuron.2008.08.013