Functional specificity of liquid-liquid phase separation at the synapse.

ABSTRACT: The mechanisms that enable synapses to achieve temporally and spatially precise signaling at nano-scale while being fluid with the cytosol are poorly understood. Liquid-liquid phase separation (LLPS) is emerging as a key principle governing subcellular organization; however, the impact of synaptic LLPS on neurotransmission is unclear. Here, using rat primary hippocampal cultures, we show that robust disruption of neuronal LLPS with aliphatic alcohols severely dysregulates action potential-dependent neurotransmission, while spontaneous neurotransmission persists. Synaptic LLPS maintains synaptic vesicle pool clustering and recycling as well as the precise organization of active zone RIM1/2 and Munc13 nanoclusters, thus supporting fast evoked Ca²⁺-dependent release. These results

SUBMITTER: Guzikowski NJ 

PROVIDER: S-EPMC11582584 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature