title: A time course of orchestrated endophilin action in sensing, bending, and stabilizing curved membranes.
abstract: Numerous proteins act in concert to sculpt membrane compartments for cell signaling and metabolism. These proteins may act as curvature sensors, membrane benders, and scaffolding molecules. Here we show that endophilin, a critical protein for rapid endocytosis, quickly transforms from a curvature sensor into an active bender upon membrane association. We find that local membrane deformation does not occur until endophilin inserts its amphipathic helices into lipid bilayers, supporting an active bending mechanism through wedging. Our time-course studies show that endophilin continues to drive membrane changes on a seconds-to-minutes time scale, indicating that the duration of endocytosis events constrains the mode of endophilin action. Finally, we find a requirement of coordinated activities between wedging and scaffolding for endophilin to produce stable membrane tubules in vitro and to promote synaptic activity in vivo. Together these data demonstrate that endophilin is a multifaceted molecule that precisely integrates activities of sensing, bending, and stabilizing curvature to sculpt membranes with speed.
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Kumud R
authors.initials: KR
authors.lastname: Poudel
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Beckman Institute, University of Illinois, Urbana, IL 61801.
authors.forename: Hang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Allen
authors.initials: A
authors.lastname: Su
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Thuong
authors.initials: T
authors.lastname: Ho
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beckman Institute, University of Illinois, Urbana, IL 61801 Department of Physics, University of Illinois, Urbana, IL 61801.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Department of Biochemistry, University of Washington, Seattle, WA 98195 jbai@fhcrc.org.
authors.forename: Jihong
authors.initials: J
authors.lastname: Bai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D008051:Lipid Bilayers / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008051:Lipid Bilayers; C504641:endophilin A1 protein, mouse