Phosphatidylserine Regulates Plasma Membrane Repair through Tetraspanin-Enriched Macrodomains

Authors

Yang E Li
Dougall M Norris
Fanqian N Xiao
Elvis Pandzic
Renee M Whan
Sandra Fok
Ming Zhou
Guangwei Du
Yang Liu
Ximing Du
Hongyuan Yang

Publication Date

6-3-2024

Journal

Journal of Cell Biology

Abstract

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from multiple sources upon plasma membrane damage. We further demonstrate that ORP9 contributes to efficient plasma membrane repair. Our results thus unveil a role for phosphatidylserine and its transfer proteins in facilitating the formation of tetraspanin-enriched macrodomains and plasma membrane repair.

Keywords

Cell Membrane, Phosphatidylserines, Tetraspanins, Humans, HeLa Cells, Membrane Proteins, Receptors, Steroid

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