| Literature DB >> 28131823 |
Chee Yeun Chung1, Vikram Khurana2, Song Yi3, Nidhi Sahni3, Ken H Loh4, Pavan K Auluck5, Valeriya Baru5, Namrata D Udeshi6, Yelena Freyzon5, Steven A Carr6, David E Hill3, Marc Vidal3, Alice Y Ting4, Susan Lindquist7.
Abstract
Synucleinopathies, including Parkinson's disease (PD), are associated with the misfolding and mistrafficking of alpha-synuclein (α-syn). Here, using an ascorbate peroxidase (APEX)-based labeling method combined with mass spectrometry, we defined a network of proteins in the immediate vicinity of α-syn in living neurons to shed light on α-syn function. This approach identified 225 proteins, including synaptic proteins, proteins involved in endocytic vesicle trafficking, the retromer complex, phosphatases and mRNA binding proteins. Many were in complexes with α-syn, and some were encoded by genes known to be risk factors for PD and other neurodegenerative diseases. Endocytic trafficking and mRNA translation proteins within this spatial α-syn map overlapped with genetic modifiers of α-syn toxicity, developed in an accompanying study (Khurana et al., this issue of Cell Systems). Our data suggest that perturbation of these particular pathways is directly related to the spatial localization of α-syn within the cell. These approaches provide new avenues to systematically examine protein function and pathology in living cells.Entities:
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Year: 2017 PMID： 28131823 PMCID： PMC5578869 DOI： 10.1016/j.cels.2017.01.002
Source DB: PubMed Journal: Cell Syst ISSN： 2405-4712 Impact factor: 10.304