MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody
MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody
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DOI：
10.1074/jbc.m007252200
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发表时间：
2001-02-23
影响因子：
4.8
通讯作者：
Kitamura, T
中科院分区：
文献类型：
--
作者：
Hirose, K;Kawashima, T;Kitamura, T
我们最近克隆了一个全长形式的mGcracGAP的cDNA.在这里，我们展示了使用抗MgcracGAP抗体，与Rho家族的其他已知间隙不同，MgcracGAP在间期定位于细胞核，在中期积累到有丝分裂纺锤体，并在胞质分裂期间凝聚在中体。N端缺失突变体的过表达导致HeLa细胞产生多核细胞。该突变体失去了定位于有丝分裂纺锤体和中体的能力。此外，还发现MgcracGAP通过其N端肌球蛋白样结构域与α、β和伽马微管蛋白结合。这些结果表明，在细胞周期进程中，MgcracGAP可能通过与微管蛋白结合而动态移动，并在胞质分裂中发挥关键作用。此外，使用GAP失活突变体，我们证明了胞质分裂需要MgcracGAP的GAP活性，这表明Rho家族的GTP酶可能是胞质分裂正常进行所必需的。
We have recently cloned a cDNA for a full-length form of MgcRacGAP. Here we show using anti-MgcRacGAP antibodies that, unlike other known GAPs for Rho family, MgcRacGAP localized to the nucleus in interphase, accumulated to the mitotic spindle in metaphase, and was condensed in the midbody during cytokinesis. Overexpression of an N-terminal deletion mutant resulted in the production of multinucleated cells in HeLa cells. This mutant lost the ability to localize in the mitotic spindle and midbody. MgcRacGAP was also found to bind alpha-, beta, and gamma -tubulins through its N-terminal myosin-like domain. These results indicate that MgcRacGAP dynamically moves during cell cycle progression probably through binding to tubulins and plays critical roles in cytokinesis, Furthermore, using a GAP-inactive mutant, we have shown that the GAP activity of MgcRacGAP is required for cytokinesis, suggesting that inactivation of the Rho family of GTPases may be required for normal progression of cytokinesis.