Work

Protein Phase Separation at the Synapse and Alpha-Synuclein Condensates

Year: 2024

Type: article

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. Furthermore, we show that αSYN condensates sequester vesicles and attract complexin-1 and -2, thus supporting a role in synaptic physiology and pathophysiology.

Source: Zenodo (CERN European Organization for Nuclear Research)

DOI: 10.5281/zenodo.14046947

Author: Lautenschläger, Janin

Institution: University of Cambridge

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: UK Research and Innovation

Award: G4879164806