Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA; Center for Integrated Protein Science CIPSM, Department Biology II, Ludwig-Maximilians University, Munich, 82152 Planegg-Martinsried, Germany.
Dev Cell. 2013 Sep 16;26(5):496-510. doi: 10.1016/j.devcel.2013.08.005. Epub 2013 Sep 5.
During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis and cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M phase, leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions.
在动物细胞胞质分裂过程中，纺锤体通过在狭窄的赤道区激活 RhoA 来指导收缩环的组装。快速 GTP 酶激活蛋白（GAP）介导的失活（RhoA 流）被认为限制了 RhoA 区的尺寸。由于不知道靶向 RhoA 的 GAP，因此测试 RhoA 流的意义受到了阻碍。在这里，我们确定有丝分裂和胞质分裂期间的 M 期 GAP（MP-GAP）是靶向 RhoA 的主要 GAP。MP-GAP 抑制导致 M 期 RhoA 的过度激活，导致大皮质突起的失控形成和后期胞质分裂失败。中心体星体的衰减加宽了 RhoA 区的宽度，但单独抑制 MP-GAP 并没有影响。同时减弱星体和抑制 MP-GAP 导致 RhoA 积聚在整个细胞周围。这些结果确定了在细胞分裂过程中限制 RhoA 的主要 GAP，并描绘了 RhoA 流和中心体星体在控制 RhoA 区尺寸方面的相对贡献。
