title: MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis.
abstract: Correct positioning of the mitotic spindle is critical to establish the correct cell-division plane. Spindle positioning involves capture of astral microtubules and generation of pushing/pulling forces at the cell cortex. Here we show that the tau-related protein MAP4 and the microtubule rescue factor CLASP1 are essential for maintaining spindle position and the correct cell-division axis in human cells. We propose that CLASP1 is required to correctly capture astral microtubules, whereas MAP4 prevents engagement of excess dynein motors, thereby protecting the system from force imbalance. Consistent with this, MAP4 physically interacts with dynein-dynactin in vivo and inhibits dynein-mediated microtubule sliding in vitro. Depletion of MAP4, but not CLASP1, causes spindle misorientation in the vertical plane, demonstrating that force generators are under spatial control. These findings have wide biological importance, because spindle positioning is essential during embryogenesis and stem-cell homeostasis.
authors.affiliation: Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Catarina P
authors.initials: CP
authors.lastname: Samora
authors.forename: Binyam
authors.initials: B
authors.lastname: Mogessie
authors.forename: Leslie
authors.initials: L
authors.lastname: Conway
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ross
authors.forename: Anne
authors.initials: A
authors.lastname: Straube
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McAinsh
mesh_terms: D002455:Cell Division; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D011485:Protein Binding; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C497850:CLASP1 protein, human; D000072159:Dynactin Complex; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D004398:Dyneins