title: MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis.
abstract: Diverse cellular processes, including multivesicular body formation, cytokinesis, and viral budding, require the sequential functions of endosomal sorting complexes required for transport (ESCRTs) 0 to III. Of these multiprotein complexes, ESCRT-III in particular plays a key role in mediating membrane fission events by forming large, ring-like helical arrays. A number of proteins playing key effector roles, most notably the ATPase associated with diverse cellular activities protein VPS4, harbor present in microtubule-interacting and trafficking molecules (MIT) domains comprising asymmetric three-helical bundles, which interact with helical MIT-interacting motifs in ESCRT-III subunits. Here we assess comprehensively the ESCRT-III interactions of the MIT-domain family member MITD1 and identify strong interactions with charged multivesicular body protein 1B (CHMP1B), CHMP2A, and increased sodium tolerance-1 (IST1). We show that these ESCRT-III subunits are important for the recruitment of MITD1 to the midbody and that MITD1 participates in the abscission phase of cytokinesis. MITD1 also dimerizes through its C-terminal domain. Both types of interactions appear important for the role of MITD1 in negatively regulating the interaction of IST1 with VPS4. Because IST1 binding in turn regulates VPS4, MITD1 may function through downstream effects on the activity of VPS4, which plays a critical role in the processing and remodeling of ESCRT filaments in abscission.
authors.affiliation: Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Seongju
authors.initials: S
authors.lastname: Lee
authors.forename: Jaerak
authors.initials: J
authors.lastname: Chang
authors.forename: Benoît
authors.initials: B
authors.lastname: Renvoisé
authors.forename: Anita
authors.initials: A
authors.lastname: Tipirneni
authors.forename: Sarah
authors.initials: S
authors.lastname: Yang
authors.forename: Craig
authors.initials: C
authors.lastname: Blackstone
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C533705:IST1 protein, human; C577154:MITD1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human