School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
Katerina Gaus Light Microscopy Facility, Mark Wainwright Analytical Center, University of New South Wales, Sydney, Australia.
J Cell Biol. 2024 Jun 3;223(6). doi: 10.1083/jcb.202307041. Epub 2024 Mar 26.
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.
质膜的完整性对于细胞功能和存活至关重要。细胞已经开发出多种机制来修复受损的质膜。在质膜修复过程中，一个关键的过程是限制损伤的大小，这是由围绕损伤部位的富含四跨膜蛋白的环的存在所促进的。在这里，我们鉴定了围绕质膜损伤部位的富含磷脂酰丝氨酸的环，类似于富含四跨膜蛋白的环。重要的是，富含磷脂酰丝氨酸和富含四跨膜蛋白的环的形成都需要磷脂酰丝氨酸及其转位蛋白 ORP5 和 ORP9。有趣的是，ORP9 而不是 ORP5 被募集到损伤部位，这表明细胞在质膜损伤后从多个来源获得磷脂酰丝氨酸。我们进一步证明 ORP9 有助于有效的质膜修复。因此，我们的研究结果揭示了磷脂酰丝氨酸及其转位蛋白在促进富含四跨膜蛋白的巨域形成和质膜修复中的作用。
