Year: 2024
Type: article
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 indicate although LLPS is necessary within the nanodomain of the synapse, the disruption of this nano-organization largely spares spontaneous neurotransmission. Therefore, properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner regulating action potential-evoked release. In this study, Guzikowski and Kavalali find properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner, creating a distinct nano-organization that facilitates subsequent synaptic signaling.
Source: Nature Communications
Authors: Natalie J. Guzikowski, Ege T. Kavalali
Institution: Vanderbilt University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
OpenAlex ID: W4404584868