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Caveolin-1 interacts with alpha-synuclein and mediates toxic actions of cellular alpha-synuclein overexpression.
MedLine Citation:
PMID:  21693152     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Caveolin-1 (Cav-1) is a transmembrane protein which clusters proteins and lipids at the cell membrane into a subclass of lipid rafts named caveolae. To increase our understanding about putative functions of Cav-1 in neuronal cells, we used mouse brain extracts and a novel technology coupling surface plasmon resonance to mass spectrometry to find binding partners to Cav-1. An interaction between Cav-1 and alpha-synclein was found and confirmed in reciprocal pulldown experiments. Genetic overexpression of alpha-synclein in mouse neuroblastoma Neuro2A cells (N2A) expectedly decreased cell survival, but also significantly increased the levels of Cav-1. Furthermore, si-RNA-mediated knockdown of Cav-1 counteracted cell death induced by overexpression of alpha-synuclein. We also used an inhibitor of proteasome (MG132) to induce cell death in a Parkinson's disease context. Cav-1 knockdown had no effect on cell death induced by MG132. Conversely, treating the cells with mevastatin, an inhibitor of cholesterol synthesis, inhibits cell death induced by MG132, but not by alpha synuclein overexpression. It can be concluded that Cav-1 may play a functional role in neuronal cells by virtue of its physical interaction with alpha-synuclein and regulate alpha synuclein-mediated actions on cell death, processes known to be involved in synucleinopathies including Parkinson's disease.
Authors:
Alexandra Madeira; Junfeng Yang; Xiaoqun Zhang; Elisabet Vikeved; Anna Nilsson; Per E Andrén; Per Svenningsson
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-13
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Center for Molecular Medicine, Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden.
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