How NINJ1 mediates plasma membrane rupture and why NINJ2 cannot
Preprint
Abstract
Summary: NINJ1 is a recently identified active executioner of plasma membrane rupture (PMR), a process previously thought to be a passive osmotic lysis event in lytic cell death. NINJ2 is a close paralog of NINJ1 but it failed to mediate PMR. By cryoEM, we found that both NINJ1 and NINJ2 were able to assemble into linear filament that binds strongly to lipids on one side but is water-soluble on the other side. The more-or-less straight NINJ1 filament was able to wrap around a membrane bleb and solubilize it from the plasma membrane to induce PMR; however, the intrinsically curved NINJ2 filament failed to do so, explaining its incapability of mediating PMR. We further demonstrated that binding to cholesterol at the inner leaflet of the lipid bilayer was responsible for the curving of the NINJ2 filament, while strong lipid binding at the outer leaflet was contributing to NINJ1’s capability of mediating PMR.Keywords
All Related Versions
- Published version: Cell, 188 (2), 292.
This publication has 37 references indexed in Scilit:
- Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosisProceedings of the National Academy of Sciences, 2012
- Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 KinaseCell, 2012
- Features and development of CootActa Crystallographica Section D Structural Biology, 2010
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa Crystallographica Section D Structural Biology, 2010
- Automated electron microscope tomography using robust prediction of specimen movementsJournal of Structural Biology, 2005
- UCSF Chimera—A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interferenceNature Genetics, 2003
- Dismantling the Cryptococcus coatTrends in Microbiology, 2001
- Decreased Resistance to Bacterial Infection and Granulocyte Defects in IAP-Deficient MiceScience, 1996
- Ninjurin, a Novel Adhesion Molecule, Is Induced by Nerve Injury and Promotes Axonal GrowthNeuron, 1996