title: ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes.
abstract: The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division.
authors.affiliation: Laboratory of Molecular Biology,  Medical Research Council, Cambridge CB2 0QH,  United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hadders
authors.forename: Monica
authors.initials: M
authors.lastname: Agromayor
authors.forename: Takayuki
authors.initials: T
authors.lastname: Obita
authors.forename: Olga
authors.initials: O
authors.lastname: Perisic
authors.forename: Anna
authors.initials: A
authors.lastname: Caballe
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kloc
authors.forename: Meindert H
authors.initials: MH
authors.lastname: Lamers
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Serrano
mesh_terms: D018360:Crystallography, X-Ray; D048749:Cytokinesis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D010739:Phospholipase D / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C577154:MITD1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010739:Phospholipase D