VAMP2 regulates phase separation of α-synuclein.
Nat Cell Biol
; 2024 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-38951707
ABSTRACT
α-Synuclein (αSYN), a pivotal synaptic protein implicated in synucleinopathies such as Parkinson's disease and Lewy body dementia, undergoes protein phase separation. We reveal that vesicle-associated membrane protein 2 (VAMP2) orchestrates αSYN phase separation both in vitro and in cells. Electrostatic interactions, specifically mediated by VAMP2 via its juxtamembrane domain and the αSYN C-terminal region, drive phase separation. Condensate formation is specific for R-SNARE VAMP2 and dependent on αSYN lipid membrane binding. Our results delineate a regulatory mechanism for αSYN phase separation in cells. Furthermore, we show that αSYN condensates sequester vesicles and attract complexin-1 and -2, thus supporting a role in synaptic physiology and pathophysiology.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Nat Cell Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido