title: Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase.
abstract: Mitotic spindle position defines the cell-cleavage site during cytokinesis. However, the mechanisms that control spindle positioning to generate equal-sized daughter cells remain poorly understood. Here, we demonstrate that two mechanisms act coordinately to center the spindle during anaphase in symmetrically dividing human cells. First, the spindle is positioned directly by the microtubule-based motor dynein, which we demonstrate is targeted to the cell cortex by two distinct pathways: a Gαi/LGN/NuMA-dependent pathway and a 4.1G/R and NuMA-dependent, anaphase-specific pathway. Second, we find that asymmetric plasma membrane elongation occurs in response to spindle mispositioning to alter the cellular boundaries relative to the spindle. Asymmetric membrane elongation is promoted by chromosome-derived Ran-GTP signals that locally reduce Anillin at the growing cell cortex. In asymmetrically elongating cells, dynein-dependent spindle anchoring at the stationary cell cortex ensures proper spindle positioning. Our results reveal the anaphase-specific spindle centering systems that achieve equal-sized cell division.
authors.affiliation: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA. tomomi.kiyomitsu@gmail.com
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kiyomitsu
authors.forename: Iain M
authors.initials: IM
authors.lastname: Cheeseman
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D000072159:Dynactin Complex; C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; C028841:erythrocyte membrane band 4.1 protein; D004398:Dyneins