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α‐Synuclein mediates alterations in membrane conductance: a potential role for α‐synuclein oligomers in cell vulnerability
Author(s) -
Feng Li Rebekah,
Federoff Howard J.,
Vicini Stefano,
MaguireZeiss Kathleen A.
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07266.x
Subject(s) - synucleinopathies , intracellular , chemistry , alpha synuclein , microbiology and biotechnology , biophysics , cell membrane , membrane , conductance , biochemistry , biology , parkinson's disease , medicine , disease , pathology , mathematics , combinatorics
α‐Synuclein has been linked to the pathogenesis of Parkinson’s disease and other synucleinopathies through its propensity to form toxic oligomers. The exact mechanism for oligomeric synuclein‐directed cell vulnerability has not been fully elucidated, but one hypothesis portends the formation of synuclein‐containing pores within cell membranes leading to leak channel‐mediated calcium influx and subsequent cell death. Here we demonstrate synuclein‐induced formation of sodium dodecyl sulfate‐stable oligomers, intracellular synuclein‐positive aggregates, alterations in membrane conductance reminiscent of leak channels and subsequent cytotoxicity in a dopaminergic‐like cell line. Furthermore we demonstrate that the synuclein‐induced membrane conductance changes are blocked by direct extracellular application of an anti‐synuclein antibody. The work presented here confirms that synuclein overexpression leads to membrane conductance changes and demonstrates for the first time through antibody‐blocking studies that synuclein plays a direct role in the formation of leak channels.