α‐Synuclein mediates alterations in membrane conductance: a potential role for α‐synuclein oligomers in cell vulnerability
Identifieur interne : 000488 ( Main/Exploration ); précédent : 000487; suivant : 000489α‐Synuclein mediates alterations in membrane conductance: a potential role for α‐synuclein oligomers in cell vulnerability
Auteurs : Li Rebekah Feng [États-Unis] ; Howard J. Federoff [États-Unis] ; Stefano Vicini [États-Unis] ; Kathleen A. Maguire-Zeiss [États-Unis]Source :
- European Journal of Neuroscience [ 0953-816X ] ; 2010-07.
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Abstract
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.
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DOI: 10.1111/j.1460-9568.2010.07266.x
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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. 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