@article{538cb059a85f498a974e608c4a81374b,
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.",
keywords = "Drosophila, F-BAR domain, Membrane, Nwk, PI(4,5)P, SH3 domain",
author = "Kelley, {Charlotte F.} and Messelaar, {Emily M.} and Eskin, {Tania L.} and Shiyu Wang and Kangkang Song and Kalanit Vishnia and Becalska, {Agata N.} and Oleg Shupliakov and Hagan, {Michael F.} and Dganit Danino and Sokolova, {Olga S.} and Daniela Nicastro and Rodal, {Avital A.}",
note = "Funding Information: Monoclonal antibodies were provided by the Developmental Studies Hybridoma Bank. We thank Bruce Goode, Brian Graziano, Mike Vahey, Shae Padrick, Tony Dinsmore, Jeff Gelles, and Jerome Fung for helpful discussions. This work was supported by an NIH/NIGMS genetics training grant (T32 GM007122 C.F.K.), a Basil O{\textquoteright}Connor Scholar Award from the March of Dimes and a Pew Scholar Award (A.A.R.), the NSF (NSF MRI DBI-1228757 to A.A.R.), a Brandeis-Leir Foundation award (A.A.R. and D.D.), NIGMS (R01GM108021 to M.F.H.), and the Swedish Research Council (13473), Parkinsonfonden, and Hj{\"a}rnfonden (to O.S.). D.D. acknowledges the support of the Russell-Berrie Nanotechnology Institute (RBNI) and the assistance of Inbal Abutbul, Ludmila Abezgauz, and Ellina Kesselman with cryo-EM imaging. Negative stain TEM experiments were performed at the User Facility Center for EM at Moscow State University. Single-particle analysis was supported by a grant from the Russian Scientific Foundation (#14-14-00234) to O.S.S. We particularly acknowledge support from the Brandeis Center for Bioinspired Soft Materials, an NSF MRSEC (DMR-1420382). Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = dec,
day = "22",
doi = "10.1016/j.celrep.2015.11.044",
language = "English (US)",
volume = "13",
pages = "2597--2609",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}