title: Molecular mechanisms of membrane deformation by I-BAR domain proteins.
abstract: BACKGROUND
  Generation of membrane curvature is critical for the formation of plasma membrane protrusions and invaginations and for shaping intracellular organelles. Among the central regulators of membrane dynamics are the BAR superfamily domains, which deform membranes into tubular structures. In contrast to the relatively well characterized BAR and F-BAR domains that promote the formation of plasma membrane invaginations, I-BAR domains induce plasma membrane protrusions through a poorly understood mechanism.
  
  
  RESULTS
  We show that I-BAR domains induce strong PI(4,5)P(2) clustering upon membrane binding, bend the membrane through electrostatic interactions, and remain dynamically associated with the inner leaflet of membrane tubules. Thus, I-BAR domains induce the formation of dynamic membrane protrusions to the opposite direction than do BAR and F-BAR domains. Strikingly, comparison of different I-BAR domains revealed that they deform PI(4,5)P(2)-rich membranes through distinct mechanisms. IRSp53 and IRTKS I-BARs bind membranes mainly through electrostatic interactions, whereas MIM and ABBA I-BARs additionally insert an amphipathic helix into the membrane bilayer, resulting in larger tubule diameter in vitro and more efficient filopodia formation in vivo. Furthermore, FRAP analysis revealed that whereas the mammalian I-BAR domains display dynamic association with filopodia, the C. elegans I-BAR domain forms relatively stable structures inside the plasma membrane protrusions.
  
  
  CONCLUSIONS
  These data define I-BAR domain as a functional member of the BAR domain superfamily and unravel the mechanisms by which I-BAR domains deform membranes to induce filopodia in cells. Furthermore, our work reveals unexpected divergence in the mechanisms by which evolutionarily distinct groups of I-BAR domains interact with PI(4,5)P(2)-rich membranes.
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, P.O. Box 56, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikangas
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.forename: Anette
authors.initials: A
authors.lastname: Pykäläinen
authors.forename: Pasi
authors.initials: P
authors.lastname: Laurinmäki
authors.forename: Pieta K
authors.initials: PK
authors.lastname: Mattila
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Butcher
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D055672:Static Electricity
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate