中国作者重要发表 - Rab11a和热休克蛋白90调节胞外α-突触核蛋白的再循环



Rab11a和热休克蛋白90调节胞外α-突触核蛋白的再循环





Rab11a and HSP90 regulate recycling of extracellular α-synuclein





Liu J., Zhang J.-P., Shi M., Quinn T., Bradner J., Beyer R., Chen S., Zhang J. 2009/5/29 18:40:20

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Journal of Neuroscience, 2009, Volume 29, Issue 5




Growing evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of Parkinson's disease (PD) and related synucleinopathies by producing neurotoxicity directly or via activation of glia. However, the mechanisms involved in the trafficking of eSNCA in neurons and/or glia remain unclear. Here, we demonstrated that eSNCA could be resecreted out of neurons via a process modulated by a recycling endosome regulator rab11a in addition to being degraded by an endosome-lysosome system. A quantitative proteomic analysis also revealed numerous proteins through which rab11a might execute its function. One of the candidate proteins, heat shock protein 90 (HSP90), was validated to be interacting with rab11a. Furthermore, geldanamycin, an HSP90 inhibitor, not only prevented resecretion of eSNCA but also attenuated neurotoxicity induced by eSNCA. Copyright © 2009 Society for Neuroscience.



Correspondence Address: Zhang, J.; Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, United States; email: zhangj@u.washington.edu



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