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Exogenous ?-synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release.

ABSTRACT: ?-Synuclein is thought to regulate neurotransmitter release through multiple interactions with presynaptic proteins, cytoskeletal elements, ion channels, and synaptic vesicles membrane. ?-Synuclein is abundant in the presynaptic compartment, and its release from neurons and glia has been described as responsible for spreading of ?-synuclein-derived pathology. ?-Synuclein-dependent dysregulation of neurotransmitter release might occur via its action on surface-exposed calcium channels. Here, we provide electrophysiological and biochemical evidence to show that ?-synuclein, applied to rat neurons in culture or striatal slices, selectively activates Cav2.2 channels, and said activation correlates with increased neurotransmitter release. Furthermore, in vivo perfusion of ?-synuclein into the striatum also leads to acute dopamine release. We further demonstrate that ?-synuclein reduces the amount of plasma membrane cholesterol and alters the partitioning of Cav2.2 channels, which move from raft to cholesterol-poor areas of the plasma membrane. We provide evidence for a novel mechanism through which ?-synuclein acts from the extracellular milieu to modulate neurotransmitter release and propose a unifying hypothesis for the mechanism of ?-synuclein action on multiple targets: the reorganization of plasma membrane microdomains.

SUBMITTER: Ronzitti G

PROVIDER: S-EPMC6802592 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Exogenous α-synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release.

Ronzitti Giuseppe G Bucci Giovanna G Emanuele Marco M Leo Damiana D Sotnikova Tatyana D TD Mus Liudmila V LV Soubrane Camille H CH Dallas Mark L ML Thalhammer Agnes A Cingolani Lorenzo A LA Mochida Sumiko S Gainetdinov Raul R RR Stephens Gary J GJ Chieregatti Evelina E

The Journal of neuroscience : the official journal of the Society for Neuroscience 20140801 32

α-Synuclein is thought to regulate neurotransmitter release through multiple interactions with presynaptic proteins, cytoskeletal elements, ion channels, and synaptic vesicles membrane. α-Synuclein is abundant in the presynaptic compartment, and its release from neurons and glia has been described as responsible for spreading of α-synuclein-derived pathology. α-Synuclein-dependent dysregulation of neurotransmitter release might occur via its action on surface-exposed calcium channels. Here, we p ...[more]

PMID: 25100594

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Dataset Information

Exogenous ?-synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release.

Publications

Exogenous α-synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release.

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