Structural basis of NINJ1-mediated plasma membrane rupture in cell death

Abstract Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture as the defining terminal event 1–7 . Plasma membrane rupture was long thought to be driven by osmotic pressure, but it has recently been shown to be in many cases an active process, mediated by the protein ninjurin-1 8 (NINJ1). Here we resolve the structure of NINJ1 and the mechanism by which it ruptures membranes. Super-resolution microscopy reveals that NINJ1 clusters into structurally diverse assemblies in the membranes of dying cells, in particular large, filamentous assemblies with branched morphology. A cryo-electron microscopy structure of NINJ1 filaments shows a tightly…

• NS
  National Science Foundation
• UB
  Universität Basel
• IO
  Institute of Science and Technology Austria
• NC
  National Center of Competence in Research AntiResist

  Award: 180541
• DF
  Deutsche Forschungsgemeinschaft

  Awards: 2075-390740016, EXC 2075-390740016, EXC 2075, 390740016
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: PP00P3_198903, 310030B_192523, 180541, 310030B_198005, 205608, 51NF40-, 51NF40-205608
• BF
  Bundesministerium für Bildung und Forschung
• UD
  Université de Lausanne
• SN
  Swiss Nanoscience Institute
• SI
  Singapore Institute of Manufacturing Technology