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Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending

journal contribution
submitted on 2024-07-02, 07:39 and posted on 2024-07-02, 07:41 authored by Houda Yasmine Ali Moussa, Kyung Chul Shin, Janarthanan Ponraj, Soo Jin Kim, Je‐Kyung Ryu, Said Mansour, Yongsoo Park

Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca2+‐dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca2+‐dependent fusion, because vesicle‐mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin‐1, a Ca2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin‐1, thereby lowering the energy barrier for Ca2+‐dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca2+‐dependent vesicle fusion by disrupting synaptotagmin‐1‐induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca2+‐dependent fusion.

Other Information

Published in: Advanced Science
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1002/advs.202206823

Additional institutions affiliated with: Core Labs - QEERI

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Neurological Disorders Research Center - QBRI
  • Qatar Environment and Energy Research Institute - HBKU

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    Qatar Biomedical Research Institute - HBKU

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