Kelley Charlotte F, Messelaar Emily M, Eskin Tania L, Wang Shiyu, Song Kangkang, Vishnia Kalanit, Becalska Agata N, Shupliakov Oleg, Hagan Michael F, Danino Dganit, Sokolova Olga S, Nicastro Daniela, Rodal Avital A
Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
Departments of Cell Biology and Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2015 Dec 22;13(11):2597-2609. doi: 10.1016/j.celrep.2015.11.044. Epub 2015 Dec 10.
F-BAR domain proteins regulate and sense membrane curvature by interacting with negatively charged phospholipids and assembling into higher-order scaffolds. However, regulatory mechanisms controlling these interactions are poorly understood. Here, we show that Drosophila Nervous Wreck (Nwk) is autoregulated by a C-terminal SH3 domain module that interacts directly with its F-BAR domain. Surprisingly, this autoregulation does not mediate a simple "on-off" switch for membrane remodeling. Instead, the isolated Nwk F-BAR domain efficiently assembles into higher-order structures and deforms membranes only within a limited range of negative membrane charge, and autoregulation elevates this range. Thus, autoregulation could either reduce membrane binding or promote higher-order assembly, depending on local cellular membrane composition. Our findings uncover an unexpected mechanism by which lipid composition directs membrane remodeling.
F-BAR结构域蛋白通过与带负电荷的磷脂相互作用并组装成高阶支架来调节和感知膜曲率。然而，控制这些相互作用的调节机制却鲜为人知。在这里，我们表明果蝇神经破坏蛋白（Nwk）由一个C端SH3结构域模块自动调节，该模块直接与其F-BAR结构域相互作用。令人惊讶的是，这种自动调节并不介导膜重塑的简单“开-关”开关。相反，分离的Nwk F-BAR结构域仅在有限的负膜电荷范围内有效地组装成高阶结构并使膜变形，而自动调节则扩大了这个范围。因此，根据局部细胞膜组成，自动调节既可以减少膜结合，也可以促进高阶组装。我们的发现揭示了一种脂质组成指导膜重塑的意外机制。
