Kelley, C.F., Messelaar, E.M., Eskin, T.L., Wang, S., Song, K., Vishnia, K., Becalska, A.N., Shupliakov, O., Hagan, M.F., Danino, D., Sokolova, O.S., Nicastro, D., Rodal, A.A. (2015). Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation.  Cell Rep. 13(11): 2597--2609.

FBrf0230460

Research paper

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.

PMC4790443 (PMC) (EuropePMC)