Fusion pore dynamics of large secretory vesicles define a distinct mechanism of exocytosis

J Cell Biol. 2023 Nov 6;222(11):e202302112. doi: 10.1083/jcb.202302112. Epub 2023 Sep 14.

Abstract

Exocrine cells utilize large secretory vesicles (LSVs) up to 10 μm in diameter. LSVs fuse with the apical surface, often recruiting actomyosin to extrude their content through dynamic fusion pores. The molecular mechanism regulating pore dynamics remains largely uncharacterized. We observe that the fusion pores of LSVs in the Drosophila larval salivary glands expand, stabilize, and constrict. Arp2/3 is essential for pore expansion and stabilization, while myosin II is essential for pore constriction. We identify several Bin-Amphiphysin-Rvs (BAR) homology domain proteins that regulate fusion pore expansion and stabilization. We show that the I-BAR protein Missing-in-Metastasis (MIM) localizes to the fusion site and is essential for pore expansion and stabilization. The MIM I-BAR domain is essential but not sufficient for localization and function. We conclude that MIM acts in concert with actin, myosin II, and additional BAR-domain proteins to control fusion pore dynamics, mediating a distinct mode of exocytosis, which facilitates actomyosin-dependent content release that maintains apical membrane homeostasis during secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Actomyosin*
  • Animals
  • Cell Membrane
  • Cytoskeletal Proteins
  • Drosophila
  • Exocytosis*
  • Secretory Vesicles* / genetics

Substances

  • Actomyosin
  • Cytoskeletal Proteins
  • MIM protein, Drosophila