Cells forming plasma membrane vesicles. Image: NIH

HK researchers reveal vesicle transport mechanism

18 May 2024

Researchers at the Hong Kong University of Science and Technology have uncovered a mechanism for short-distance vesicle transport within cells, driven by protein phase separation. This discovery sheds light on how vesicles, crucial for cellular function, move locally without the aid of molecular motors.Vesicles, the cellular containers responsible for transporting materials such as proteins and lipids and recycling waste, are known to travel long distances using molecular motors. However, the exact mechanisms for short-distance transport within specific cell regions were unclear.

The study, led by Hua Qiu and Xiandeng Wu of the HKUST Division of Life Sciences, reveals that phase separation of synaptic proteins can facilitate the regulated, directional transport of synaptic vesicles within presynaptic boutons. Specifically, the large scaffold protein Piccolo (Pclo) plays a central role in this process. Upon sensing calcium ions (Ca2+), Pclo extracts synaptic vesicles from the synapsin-clustered reserve pool and deposits them onto the surface of the active zone protein condensate. This mechanism ensures the precise delivery of synaptic vesicles to neurotransmitter release sites.

Hua Qiu (left) and Dr Xiandeng Wu (right)

The HKUST team also identified the involvement of the Trk-fused gene in phase separation-mediated vesicle trafficking from the endoplasmic reticulum to the Golgi apparatus. These findings suggest that phase separation may be a general principle underlying short-distance vesicle transport in cells.

“Our study demonstrates that short-distance and directional transport of vesicles can occur through phase separation of vesicles with protein condensates, without the involvement of molecular motors. It expands our understanding of cellular logistics and suggests ways to explore how cells maintain efficiency and order at the microscopic level,” explained Professor Mingjie Zhang, leader of the group and the recipient of two Croucher Senior Research Fellowships (2003 and 2018).

The findings were published in the scientific journal Cell.