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

doi:10.1016/j.neuron.2008.08.013

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 revista › Artículo › revisión 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 original	English
Páginas (desde-hasta)	97-110
Número de páginas	14
Publicación	Neuron
Volumen	60
N.º	1
DOI	https://doi.org/10.1016/j.neuron.2008.08.013
Estado	Published - oct. 9 2008
Publicado de forma externa	Sí

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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10.1016/j.neuron.2008.08.013

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title = "HSP90β Regulates Rapsyn Turnover and Subsequent AChR Cluster Formation and Maintenance",

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.",

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

note = "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.). ",

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AU - Luo, Shiwen

AU - Zhang, Bin

AU - Dong, Xian ping

AU - Tao, Yanmei

AU - Ting, Annie

AU - Zhou, Zheng

AU - Meixiong, James

AU - Luo, Junjie

AU - Chiu, F. C.Alex

AU - Xiong, Wen C.

AU - Mei, Lin

N1 - 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.).

PY - 2008/10/9

Y1 - 2008/10/9

N2 - 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.

AB - 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.

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HSP90β Regulates Rapsyn Turnover and Subsequent AChR Cluster Formation and Maintenance

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

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