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Rab11a and HSP90 regulate recycling of extracellular alpha-synuclein.

ABSTRACT: Growing evidence suggests that extracellular alpha-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.

SUBMITTER: Liu J

PROVIDER: S-EPMC3241981 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Rab11a and HSP90 regulate recycling of extracellular alpha-synuclein.

Liu Jun J Zhang Jian-Peng JP Shi Min M Quinn Thomas T Bradner Joshua J Beyer Richard R Chen Shengdi S Zhang Jing J

The Journal of neuroscience : the official journal of the Society for Neuroscience 20090201 5

Growing evidence suggests that extracellular alpha-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 ...[more]

PMID: 19193894

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