美国哈佛医学院吴皓课题组发现，NINJ1通过切割和释放膜盘介导质膜破裂。这一研究成果于2024年4月12日在线发表在国际学术期刊《细胞》上。

研究人员报告了由NINJ1环分割而成的NINJ1寡聚体的冷冻电镜结构。每个NINJ1亚基都包括两性螺旋（?1, ?2）和跨膜（TM）螺旋（?3, ?4），并形成一个亚基链，主要由TM螺旋和?1组成。?3和?4是扭结的，Gly残基对功能很重要。NINJ1寡聚体有一个凹的疏水侧，应该面向膜，还有一个凸的亲水侧由?1和?2形成，可能是在活化时形成的。

这一结构观察结果表明，NINJ1可以形成膜盘，这与重组NINJ1的膜破碎一致。活细胞和超分辨率成像发现了质膜上的环状结构，这些结构被释放到培养上清液中。如脂质染色所示，释放的NINJ1包围着内部的膜。因此，NINJ1介导的膜盘形成不同于gasdermin介导的孔形成，后者会导致膜脱落和质膜破裂。

据介绍，膜蛋白NINJ1在焦亡和其他裂解性细胞死亡途径中介导质膜破裂。

附：英文原文

Title: NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks

Author: Liron David, Jazlyn P. Borges, L. Robert Hollingsworth, Allen Volchuk, Isabelle Jansen, Evelyn Garlick, Benjamin E. Steinberg, Hao Wu

Issue&Volume: 2024-04-12

Abstract: The membrane protein NINJ1 mediates plasma membrane rupture in pyroptosis and otherlytic cell death pathways. Here, we report the cryo-EM structure of a NINJ1 oligomersegmented from NINJ1 rings. Each NINJ1 subunit comprises amphipathic (1, 2) andtransmembrane (TM) helices (3, 4) and forms a chain of subunits, mainly by the TMhelices and 1. 3 and 4 are kinked, and the Gly residues are important for function.The NINJ1 oligomer possesses a concave hydrophobic side that should face the membraneand a convex hydrophilic side formed by 1 and 2, presumably upon activation. Thisstructural observation suggests that NINJ1 can form membrane disks, consistent withmembrane fragmentation by recombinant NINJ1. Live-cell and super-resolution imaginguncover ring-like structures on the plasma membrane that are released into the culturesupernatant. Released NINJ1 encircles a membrane inside, as shown by lipid staining.Therefore, NINJ1-mediated membrane disk formation is different from gasdermin-mediatedpore formation, resulting in membrane loss and plasma membrane rupture.

DOI: 10.1016/j.cell.2024.03.008

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00300-3