Authors: | Kelley, CF; Messelaar, EM; Eskin, TL; Wang, SY; Song, KK; Vishnia, K; Becalska, AN; Shupliakov, O; Hagan, MF; Danino, D; Sokolova, OS; Nicastro, D; Rodal, AA |
Year: | 2015 |
Journal: | Cell Reports 13: 2597-2609 Article Link (DOI) PubMed |
Title: | Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation |
Abstract: | 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. |
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