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.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Kelley
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Messelaar
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Tania L
authors.initials: TL
authors.lastname: Eskin
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Departments of Cell Biology and Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Kalanit
authors.initials: K
authors.lastname: Vishnia
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Agata N
authors.initials: AN
authors.lastname: Becalska
authors.affiliation: Department of Neuroscience, Karolinska Institutet, von Eulers väg 3, 171 77 Stockholm, Sweden.
authors.forename: Oleg
authors.initials: O
authors.lastname: Shupliakov
authors.affiliation: Martin Fisher School of Physics, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hagan
authors.affiliation: Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
authors.affiliation: Department of Bioengineering, Faculty of Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Sokolova
authors.affiliation: Departments of Cell Biology and Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nicastro
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: arodal@brandeis.edu.
authors.forename: Avital A
authors.initials: AA
authors.lastname: Rodal
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D018613:Microscopy, Confocal; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008081:Liposomes; D010743:Phospholipids
keywords: Drosophila; F-BAR domain; Nwk; PI(4,5)P(2); SH3 domain; membrane