Simunovic Mijo, Manneville Jean-Baptiste, Renard Henri-François, Evergren Emma, Raghunathan Krishnan, Bhatia Dhiraj, Kenworthy Anne K, Voth Gregory A, Prost Jacques, McMahon Harvey T, Johannes Ludger, Bassereau Patricia, Callan-Jones Andrew
Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France; Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, The University of Chicago, 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
Subcellular Structure and Cellular Dynamics Unit, Institut Curie, PSL Research University, CNRS UMR144, 75005 Paris, France.
Cell. 2017 Jun 29;170(1):172-184.e11. doi: 10.1016/j.cell.2017.05.047. Epub 2017 Jun 22.
Membrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis. We call this mechanism friction-driven scission (FDS). In cells, motors pull tubes, particularly during endocytosis. Through reconstitution, we show that motors not only can pull out and extend protein-scaffolded tubes but also can cut them by FDS. FDS is generic, operating even in the absence of amphipathic helices in the BAR domain, and could in principle apply to any high-friction protein and membrane assembly.
膜分裂对于细胞内运输至关重要。虽然诸如内吞素等BAR结构域蛋白已被报道参与管状膜颈部的非发动蛋白依赖性分裂，但切割机制尚未被破解。在此，我们结合理论模型、体外和体内实验，揭示了蛋白质支架如何切割管状膜。我们证明，与下层管结合的蛋白质支架为脂质扩散创造了摩擦屏障；管的伸长因此建立局部膜张力，直到膜通过裂解发生分裂。我们将这种机制称为摩擦驱动分裂（FDS）。在细胞中，马达拉动管子，特别是在胞吞作用期间。通过重组，我们表明马达不仅可以拉出并延伸蛋白质支架化的管子，还可以通过FDS切割它们。FDS是通用的，即使在BAR结构域中不存在两亲性螺旋的情况下也能起作用，并且原则上可以应用于任何高摩擦蛋白质和膜组装体。
