Abstract 1538 Phosphatidylserine regulates plasma membrane repair through the assembly of tetraspanin-enriched macrodomains

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 the 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. This work is supported by the National Health and Medical Research Council, Australia, and by UTH Houston.