Concerted actions of distinct nonmuscle myosin II isoforms drive intracellular membrane remodeling in live animals

Author:

Milberg Oleg1,Shitara Akiko21,Ebrahim Seham2,Masedunskas Andrius13ORCID,Tora Muhibullah1,Tran Duy T.4,Chen Yun2,Conti Mary Anne5,Adelstein Robert S.5ORCID,Ten Hagen Kelly G.4,Weigert Roberto21ORCID

Affiliation:

1. Intracellular Membrane Trafficking Section, National Institutes of Health, Bethesda, MD

2. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

3. School of Medical Sciences, University of New South Wales, Sidney, Australia

4. Developmental Glycobiology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD

5. Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

Abstract

Membrane remodeling plays a fundamental role during a variety of biological events. However, the dynamics and the molecular mechanisms regulating this process within cells in mammalian tissues in situ remain largely unknown. In this study, we use intravital subcellular microscopy in live mice to study the role of the actomyosin cytoskeleton in driving the remodeling of membranes of large secretory granules, which are integrated into the plasma membrane during regulated exocytosis. We show that two isoforms of nonmuscle myosin II, NMIIA and NMIIB, control distinct steps of the integration process. Furthermore, we find that F-actin is not essential for the recruitment of NMII to the secretory granules but plays a key role in the assembly and activation of NMII into contractile filaments. Our data support a dual role for the actomyosin cytoskeleton in providing the mechanical forces required to remodel the lipid bilayer and serving as a scaffold to recruit key regulatory molecules.

Funder

National Institutes of Health

National Cancer Institute

National Institute of Dental and Craniofacial Research

Publisher

Rockefeller University Press

Subject

Cell Biology

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