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

Tom Biton; Nadav Scher; Shari Carmon; Yael Elbaz-Alon; Eyal D. Schejter; Ben-Zion Shilo; Ori Avinoam

doi:10.1083/jcb.202302112

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

Tom Biton, Nadav Scher, Shari Carmon, Yael Elbaz-Alon, Eyal D. Schejter, Ben-Zion Shilo^*, Ori Avinoam^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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	https://doi.org/10.1083/jcb.202302112
Publication status	Published - 6 Nov 2023

Funding

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.

All Science Journal Classification (ASJC) codes

Cell Biology

Access to Document

10.1083/jcb.202302112Licence: CC BY

Cite this

@article{b149e42caa5b4111b67f2f90b2979f61,

title = "Fusion pore dynamics of large secretory vesicles define a distinct mechanism of exocytosis",

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.",

author = "Tom Biton and Nadav Scher and Shari Carmon and Yael Elbaz-Alon and Schejter, \{Eyal D.\} and Ben-Zion Shilo and Ori Avinoam",

note = "Publisher Copyright: {\textcopyright} 2023 Biton et al.",

year = "2023",

month = nov,

day = "6",

doi = "10.1083/jcb.202302112",

language = "English",

volume = "222",

journal = "Journal of Cell Biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

number = "11",

}

TY - JOUR

T1 - Fusion pore dynamics of large secretory vesicles define a distinct mechanism of exocytosis

AU - Biton, Tom

AU - Scher, Nadav

AU - Carmon, Shari

AU - Elbaz-Alon, Yael

AU - Schejter, Eyal D.

AU - Shilo, Ben-Zion

AU - Avinoam, Ori

PY - 2023/11/6

Y1 - 2023/11/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85171233215

U2 - 10.1083/jcb.202302112

DO - 10.1083/jcb.202302112

M3 - Article

SN - 0021-9525

VL - 222

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 11

M1 - e202302112

ER -

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

Abstract

Funding

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this