Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, Paris, France.
Sorbonne Université, Paris, France.
Elife. 2018 Sep 20;7:e37262. doi: 10.7554/eLife.37262.
One challenge in cell biology is to decipher the biophysical mechanisms governing protein enrichment on curved membranes and the resulting membrane deformation. The ERM protein ezrin is abundant and associated with cellular membranes that are flat, positively or negatively curved. Using and cell biology approaches, we assess mechanisms of ezrin's enrichment on curved membranes. We evidence that wild-type ezrin (ezrinWT) and its phosphomimetic mutant T567D (ezrinTD) do not deform membranes but self-assemble anti-parallelly, zipping adjacent membranes. EzrinTD's specific conformation reduces intermolecular interactions, allows binding to actin filaments, which reduces membrane tethering, and promotes ezrin binding to positively-curved membranes. While neither ezrinTD nor ezrinWT senses negative curvature alone, we demonstrate that interacting with curvature-sensing I-BAR-domain proteins facilitates ezrin enrichment in negatively-curved membrane protrusions. Overall, our work demonstrates that ezrin can tether membranes, or be targeted to curved membranes, depending on conformations and interactions with actin and curvature-sensing binding partners.
细胞生物学的一个挑战是破译控制蛋白质在弯曲膜上富集的生物物理机制，以及由此产生的膜变形。ERM 蛋白 ezrin 丰富存在于扁平的、正曲率或负曲率的细胞膜上。我们利用 和细胞生物学方法来评估 ezrin 在弯曲膜上富集的机制。我们证明野生型 ezrin（ezrinWT）及其磷酸模拟突变体 T567D（ezrinTD）不会使膜变形，而是反平行自组装，将相邻的膜扎在一起。ezrinTD 的特定构象减少了分子间相互作用，允许与肌动蛋白丝结合，从而减少膜连接，并促进 ezrin 与正曲率膜结合。虽然 ezrinTD 和 ezrinWT 都不能单独感知负曲率，但我们证明与曲率感应 I-BAR 结构域蛋白相互作用有助于 ezrin 在负曲率膜突起中富集。总的来说，我们的工作表明，ezrin 可以根据与肌动蛋白和曲率感应结合伙伴的构象和相互作用来连接膜，或靶向弯曲的膜。
