Short-distance vesicle transport via phase separation

Abstract

In addition to directional and long-distance transport achieved by motor proteins and cytoskeleton, cellular vesicles also need to be rapidly moved at short distances in subcellular compartments with defined directions and precise regulations to meet various cellular functions. Such short-distance vesicle transport is not known to involve molecular motors, while free diffusion lacks directions and regulation. The exact mechanisms for this short-distance transport remain mysterious. Here, using synaptic vesicle (SV) transport as a paradigm, we demonstrate that protein phase separation with synaptic vesicles can facilitate regulated and directional vesicle transport between different sub-compartments of presynaptic boutons. Specifically, the large coiled-coil scaffold protein Piccolo, in response to Ca²⁺ and through its C2A domain-mediated Ca²⁺ sensing, is capable of extracting SVs from the synapsin-clustered reserve pool condensate and depositing them onto the surface of the active zone protein condensate. Besides, we further show that Trk-fused gene (TFG) can co-acervate with COPII vesicle and mediate its transport from ER to ER-Golgi intermediate compartment in a cytoskeleton independent manner. Therefore, we propose that phase separation may have a ubiquitous role in mediating short-distance, directional vesicle transport within cellular systems

Date of Award	2024
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Zhenguo WU (Supervisor) & Mingjie ZHANG (Supervisor)