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

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

70 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)97-110
Número de páginas14
PublicaciónNeuron
Volumen60
N.º1
DOI
EstadoPublished - oct. 9 2008
Publicado de forma externa

Nota bibliográfica

Funding Information:
We thank Dr. Tadaomi Takenawa for HSP90 constructs, Dr. David Toft for HSP90β protein, Dr. Rick Rotundo and Dr. Jon Lindstrom for AChR antibodies, Dr. Ezekiel Carpenter-Hyland for assistance with imaging analysis, Ms. Hannah Neiswender for technical assistance, and Mr. Eric Miller and the Proteomics Core of Medical College of Georgia for assistance with proteomics analysis. This work is support in part by grants from NIH (L.M. and W.C.X) and Muscular Dystrophy Association (L.M.).

ASJC Scopus Subject Areas

  • General Neuroscience

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