title: Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.
abstract: The tunneling nanotube (TNT) is a structure used for intercellular communication, and is a thin membrane protrusion mediating transport of various signaling molecules and cellular components. M-Sec has potent membrane deformation ability and induces TNT formation in cooperation with the Ral/exocyst complex. Here, we show that the N-terminal polybasic region of M-Sec directly binds phosphatidylinositol (4,5)-bisphosphate for its localization to the plasma membrane during the initial stage of TNT formation. We further report a crystal structure of M-Sec, which consists of helix bundles arranged in a straight rod-like shape, similar to the membrane tethering complex subunits. A positively charged surface in the C-terminal domains is required for M-Sec interaction with active RalA to extend the plasma membrane protrusions. Our results suggest that the membrane-associated M-Sec recruits active RalA, which directs the exocyst complex to form TNTs.
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.|Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8501, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamakami-Kimura
authors.affiliation: Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamagata
authors.affiliation: Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, N-21, W-11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobashigawa
authors.affiliation: Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, N-21, W-11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Amada
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.|Division of Biochemistry, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.|Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.|Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8501, Japan.|CREST, JST, Saitama 332-0012, Japan.
authors.forename: Shuya
authors.initials: S
authors.lastname: Fukai