CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis.
CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis.
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CYK-4：中央纺锤体形成和细胞因子所需的RHO家族GTPase激活蛋白（GAP）。
DOI：
10.1083/jcb.149.7.1391
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发表时间：
2000-06-26
影响因子：
7.8
通讯作者：
Glotzer, M
中科院分区：
文献类型：
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作者：
Jantsch-Plunger, V;Gonczy, P;Romano, A;Schnabel, H;Hamill, D;Schnabel, R;Hyman, A A;Glotzer, M
在动物细胞的胞质分裂过程中，有丝分裂纺锤体至少起两种作用。最初，纺锤体定位收缩环。随后，由后期形成的微管束组成的中央纺锤体促进胞质分裂的后期步骤。中央纺锤体在胞质分裂中是如何组装和发挥作用的，目前还知之甚少。cyk-4基因已在秀丽隐杆线虫中通过遗传分析鉴定。来自cyk-4（t1689 ts）突变雌雄同体的胚胎开始，但不能完成胞质分裂。这些胚胎也无法组装中央纺锤体。我们发现，cyk-4基因编码的GT3激活蛋白（GAP）的Rho家族GTPases。CYK-4在体外通过RhoA、Rac 1和Cdc 42激活GTP水解。RNA介导的RhoA、Rac 1和Cdc 42的干扰表明，只有RhoA是胞质分裂所必需的，因此，RhoA可能是胞质分裂的CYK-4 GAP活性的靶点。CYK-4和CYK-4：GFP融合蛋白定位于中央纺锤体并在细胞分裂残余物处持续存在。CYK-4定位依赖于驱动蛋白样蛋白ZEN-4/CeMKLP 1，反之亦然。这些数据表明CYK-4和ZEN-4/CeMKLP 1在中央纺锤体组装中协同作用。CYK-4的纺锤体定位可以加速RhoA对GTP的水解，从而使收缩环解体并完成胞质分裂。
During cytokinesis of animal cells, the mitotic spindle plays at least two roles. Initially, the spindle positions the contractile ring. Subsequently, the central spindle, which is composed of microtubule bundles that form during anaphase, promotes a late step in cytokinesis. How the central spindle assembles and functions in cytokinesis is poorly understood. The cyk-4 gene has been identified by genetic analysis in Caenorhabditis elegans. Embryos from cyk-4(t1689ts) mutant hermaphrodites initiate, but fail to complete, cytokinesis. These embryos also fail to assemble the central spindle. We show that the cyk-4 gene encodes a GTPase activating protein (GAP) for Rho family GTPases. CYK-4 activates GTP hydrolysis by RhoA, Rac1, and Cdc42 in vitro. RNA-mediated interference of RhoA, Rac1, and Cdc42 indicates that only RhoA is essential for cytokinesis and, thus, RhoA is the likely target of CYK-4 GAP activity for cytokinesis. CYK-4 and a CYK-4:GFP fusion protein localize to the central spindle and persist at cell division remnants. CYK-4 localization is dependent on the kinesin-like protein ZEN-4/CeMKLP1 and vice versa. These data suggest that CYK-4 and ZEN-4/CeMKLP1 cooperate in central spindle assembly. Central spindle localization of CYK-4 could accelerate GTP hydrolysis by RhoA, thereby allowing contractile ring disassembly and completion of cytokinesis.