title: Caveolin-1 interacts with alpha-synuclein and mediates toxic actions of cellular alpha-synuclein overexpression.
abstract: 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.affiliation: Center for Molecular Medicine, Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden. alexandra.madeira@hotmail.fr
authors.forename: Alexandra
authors.initials: A
authors.lastname: Madeira
authors.forename: Junfeng
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vikeved
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.forename: Per E
authors.initials: PE
authors.lastname: Andrén
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D034741:RNA, Small Interfering; D020349:Surface Plasmon Resonance; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D017931:DNA Primers; D034741:RNA, Small Interfering; D051844:alpha-Synuclein