Centre for Mechanochemical Cell Biology, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
Nat Cell Biol. 2011 Aug 7;13(9):1040-50. doi: 10.1038/ncb2297.
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.
正确定位有丝分裂纺锤体对于建立正确的细胞分裂平面至关重要。纺锤体定位涉及星体微管的捕获以及在细胞质皮层产生推/拉力。在这里，我们表明，与微管相关的 MAP4 蛋白和微管挽救因子 CLASP1 对于维持人类细胞中的纺锤体位置和正确的细胞分裂轴是必不可少的。我们提出，CLASP1 是正确捕获星体微管所必需的，而 MAP4 防止过度的动力蛋白马达的参与，从而保护该系统免受力不平衡的影响。与此一致的是，MAP4 在体内与动力蛋白-动力蛋白复合物相互作用，并在体外抑制动力蛋白介导的微管滑动。MAP4 的耗竭而非 CLASP1 的耗竭导致纺锤体在垂直平面上的错位，表明力发生器受到空间控制。这些发现具有广泛的生物学重要性，因为纺锤体定位在胚胎发生和干细胞稳态中至关重要。
