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.
| Original language | English |
|---|---|
| Article number | e202302112 |
| Number of pages | 29 |
| Journal | Journal of Cell Biology |
| Volume | 222 |
| Issue number | 11 |
| Early online date | 14 Sept 2023 |
| DOIs | |
| Publication status | Published - 6 Nov 2023 |
Bibliographical note
We thank Prof. Sven Bogdan (Philipps-University Marburg, Marburg, Germany) for the UAS-CIP4-EGFP Drosophila line, Dr. Helen Zenner (University of Cambridge, Cambridge, UK) for the MIMNullDrosophila line, and Prof. Julie Brill (University of Toronto, Toronto, Canada) for the Sgs3-DsRed Drosophila line. We thank the EM Unit of the Weizmann Institute for assistance. We thank all members of the O. Avinoam and B.-Z. Shilo labs for fruitful comments and discussions.This research was supported by the Israel Science Foundation (grant no. 706/20) to B.-Z. Shilo, O. Avinoam, and E.D. Schejter, and the Minerva Foundation with funding from the Federal German Ministry for Education and Research. O. Avinoam also acknowledges funding from the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, the Schwartz Reisman Collaborative Science Program, the Yeda-Sela Center for Basic Research, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no 851080). O. Avinoam is an incumbent of the Miriam Berman presidential development chair. B.-Z. Shilo is an incumbent of the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics.