title: Mip1 associates with both the Mps1 kinase and actin, and is required for cell cortex stability and anaphase spindle positioning.
abstract: The Mps1 family of protein kinases contributes to cell cycle control by regulating multiple microtubule cytoskeleton activities. We have uncovered a new Mps1 substrate that provides a novel link between Mps1 and the actin cytoskeleton. We have identified a conserved human Mps1 (hMps1) interacting protein we have termed Mps1 interacting protein-1 (Mip1). Mip1 defines an uncharacterized family of conserved proteins that contain coiled-coil and calponin homology domains. We demonstrate that Mip1 is a phosphoprotein that interacts with hMps1 in vitro and in vivo and is a hMps1 substrate. Mip1 exhibits dynamic localization during the cell cycle; Mip1 localizes to the actin cytoskeleton during interphase, the spindle in early mitosis, and the cleavage furrow during cytokinesis. Mip1 function is required to ensure proper spindle positioning at the onset of anaphase after cells begin furrow ingression. Cells depleted of Mip1 exhibit aberrant mitotic actin filament organization, excessive membrane blebbing, dramatic spindle rocking, and chromosome distribution errors during early cytokinesis producing high numbers of binucleate cells. Our data indicate that Mip1 is a newly recognized component of the actin cytoskeleton that interacts with hMps1 and that it is essential to ensure proper segregation of the genome during cell cleavage.
authors.affiliation: Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Mattison
authors.forename: Jason
authors.initials: J
authors.lastname: Stumpff
authors.forename: Linda
authors.initials: L
authors.lastname: Wordeman
authors.forename: Mark
authors.initials: M
authors.lastname: Winey
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000705:Anaphase; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000648:ultrastructure; D020798:Two-Hybrid System Techniques
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C493277:MAPKAP1 protein, human; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human