Local PI(4,5)P2 signaling inhibits fusion pore expansion during exocytosis

Abstract

Phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) is an important signaling phospholipid that is required for regulated exocytosis and some forms of endocytosis. The two processes share a topologically similar pore structure that connects the vesicle lumen with the outside. Widening of the fusion pore during exocytosis leads to cargo release, while its closure initiates kiss&run or cavicapture endocytosis. We show here, using live-cell total internal reflection fluorescence (TIRF) microscopy of insulin granule exocytosis, that transient accumulation of PI(4,5)P2 at the release site recruits components of the endocytic fission machinery and stalls the late fusion pore expansion that is required for peptide release. The absence of clathrin differentiates this mechanism from clathrin-mediated endocytosis. Knockdown of phosphatidylinositol-phosphate-5-ki-nase-1c or optogenetic recruitment of 5-phosphatase reduces PI(4,5)P2 transients and accelerates fusion pore expansion, suggesting that acute PI(4,5)P2 synthesis is involved. Thus, local phospholipid signaling in-hibits fusion pore expansion and peptide release through an unconventional endocytic mechanism.

Published in

Cell Reports
2023, volume: 42, number: 2, article number: 112036
Publisher: CELL PRESS

SLU Authors

• Omar Hmeadi, Muhmmad

  • Uppsala University

UKÄ Subject classification

Cell and Molecular Biology

Publication identifier

• DOI: https://doi.org/10.1016/j.celrep.2023.112036

Permanent link to this page (URI)

https://res.slu.se/id/publ/131976