The septin cytoskeleton is required for plasma membrane repair.

Autor:	Prislusky MI; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Lam JGT; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Contreras VR; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.; Grupo Investigaciones Biomédicas, Universidad de Sucre, Sincelejo, Sucre, Colombia., Ng M; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Chamberlain M; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Pathak-Sharma S; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Fields M; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Zhang X; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA., Amer AO; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA., Seveau S; Department of Microbial Infection & Immunity, Wexner Medical Center, The Ohio State University, Columbus, OH, USA. Seveau.1@osu.edu.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Sep; Vol. 25 (9), pp. 3870-3895. Date of Electronic Publication: 2024 Jul 05.
DOI:	10.1038/s44319-024-00195-6
Abstrakt:	Plasma membrane repair is a fundamental homeostatic process of eukaryotic cells. Here, we report a new function for the conserved cytoskeletal proteins known as septins in the repair of cells perforated by pore-forming toxins or mechanical disruption. Using a silencing RNA screen, we identified known repair factors (e.g. annexin A2, ANXA2) and novel factors such as septin 7 (SEPT7) that is essential for septin assembly. Upon plasma membrane injury, the septin cytoskeleton is extensively redistributed to form submembranous domains arranged as knob and loop structures containing F-actin, myosin IIA, S100A11, and ANXA2. Formation of these domains is Ca 2+ -dependent and correlates with plasma membrane repair efficiency. Super-resolution microscopy revealed that septins and F-actin form intertwined filaments associated with ANXA2. Depletion of SEPT7 prevented ANXA2 recruitment and formation of submembranous actomyosin domains. However, ANXA2 depletion had no effect on domain formation. Collectively, our data support a novel septin-based mechanism for resealing damaged cells, in which the septin cytoskeleton plays a key structural role in remodeling the plasma membrane by promoting the formation of SEPT/F-actin/myosin IIA/ANXA2/S100A11 repair domains. (© 2024. The Author(s).)
Databáze:	MEDLINE
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