在有丝分裂激酶的控制下，GEF-H1在胞质分裂过程中调节局部RhoA激活。
GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases.
作者信息
Birkenfeld Jörg, Nalbant Perihan, Bohl Benjamin P, Pertz Olivier, Hahn Klaus M, Bokoch Gary M
机构信息
Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Dev Cell. 2007 May;12(5):699-712. doi: 10.1016/j.devcel.2007.03.014.
Formation of the mitotic cleavage furrow is dependent upon both microtubules and activity of the small GTPase RhoA. GEF-H1 is a microtubule-regulated exchange factor that couples microtubule dynamics to RhoA activation. GEF-H1 localized to the mitotic apparatus in HeLa cells, particularly at the tips of cortical microtubules and the midbody, and perturbation of GEF-H1 function induced mitotic aberrations, including asymmetric furrowing, membrane blebbing, and impaired cytokinesis. The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity. Dephosphorylation of GEF-H1 occurs just prior to cytokinesis, accompanied by GEF-H1-dependent GTP loading on RhoA. Using a live cell biosensor, we demonstrate distinct roles for GEF-H1 and Ect2 in regulating Rho activity in the cleavage furrow, with GEF-H1 catalyzing Rho activation in response to Ect2-dependent localization and initiation of cell cleavage. Our results identify a GEF-H1-dependent mechanism to modulate localized RhoA activation during cytokinesis under the control of mitotic kinases.
有丝分裂分裂沟的形成依赖于微管和小GTP酶RhoA的活性。GEF-H1是一种微管调节的交换因子，它将微管动力学与RhoA激活联系起来。GEF-H1定位于HeLa细胞的有丝分裂装置，特别是在皮质微管的末端和中体，GEF-H1功能的扰动会诱导有丝分裂异常，包括不对称缢缩、膜泡形成和胞质分裂受损。有丝分裂激酶Aurora A/B和Cdk1/Cyclin B使GEF-H1磷酸化，从而抑制GEF-H1的催化活性。GEF-H1的去磷酸化发生在胞质分裂之前，同时伴随着RhoA上依赖于GEF-H1的GTP加载。使用活细胞生物传感器，我们证明了GEF-H1和Ect2在调节分裂沟中Rho活性方面的不同作用，GEF-H1响应Ect2依赖的定位和细胞分裂的启动催化Rho激活。我们的结果确定了一种在有丝分裂激酶控制下，在胞质分裂过程中调节局部RhoA激活的GEF-H1依赖机制。
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