Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

54-POS Board 18 ACTIVE SYNTAXIN IS SORTED FROM RESERVOIR CLUSTERS FOR SYNAPTIC VESICLE FUSION

Jiajie Diao 1 ; 1 University of Cincinnati College of Medicine, Cincinnati, OH, USA

The SNARE protein syntaxin mediates neuronal exocytosis and self-assembles into large clusters in the plasma membrane. The formation and function of these clusters, and whether they promote or inhibit synaptic vesicle fusion remain unclear. Here, using optogenetic control of syntaxin clustering in vitro and in vivo, we show that clustering reduces both spontaneous and triggered vesicle fusion, and this impairs mouse hunting behavior. Cluster formation is promoted by liquid-liquid phase separation of the cytoplasmic domain of syntaxin. For the regulatory mechanism, Munc18, which is known to alter syntaxin conformation, acts to reduce cluster formation, promoting active syntaxin. These results suggest exocytosis regulation involves phase separation-induced syntaxin clusters that serve as a syntaxin reservoir, while Munc18 releases syntaxin monomers for enhanced fusion.

111