Regulation of cytokinesis by Rho GTPase flux.

Regulation of cytokinesis by Rho GTPase flux.
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DOI:
10.1038/ncb1814
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发表时间:
2009-01
影响因子:
21.3
通讯作者:
Bement, William M.
Bement, William M.
中科院分区:
生物学1区
文献类型:
--
作者:
Miller, Ann L.;Bement, William M.

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在动物细胞中,胞质分裂由肌动蛋白丝(F-肌动蛋白)和肌球蛋白-2的收缩环提供动力。收缩环的形成依赖于小的GTdR,RhoA,其在细胞赤道的精确区域中被激活。长期以来,人们一直认为胞质分裂和其他Rho依赖性过程是以顺序的方式控制的,其中通过鸟嘌呤核苷酸交换因子(GEF)的Rho激活启动特定事件,并且通过GTP酶激活蛋白(GAP)的Rho失活终止该事件。MgcRacGAP是一种保守的胞质分裂调节因子,被认为仅在胞质分裂结束时需要。在这里,我们表明,MgcRacGAP的GAP活动是必要的早期在胞质分裂的形成和维持的Rho活性区。通过点突变破坏GAP活性导致Rho活性区集中性差,而差距结构域的完全去除导致显示横向不稳定性和/或快速侧到侧振荡的非集中区。我们提出MgcRacGAP差距域在整个胞质分裂过程中起着两个意想不到的作用:第一,它短暂地锚定活性Rho,第二,它促进局部Rho失活,导致Rho通过GTdR循环的恒定通量。
In animal cells, cytokinesis is powered by a contractile ring of actin filaments (F-actin) and myosin-2. Formation of the contractile ring is dependent on the small GTPase, RhoA, which is activated in a precise zone at the cell equator. It has long been assumed that cytokinesis and other Rho-dependent processes are controlled in a sequential manner, whereby Rho activation via guanine nucleotide exchange factors (GEFs) initiates a particular event, and Rho inactivation via GTPase activating proteins (GAPs) terminates that event. MgcRacGAP is a conserved cytokinesis regulator thought to be required only at the end of cytokinesis. Here we show that MgcRacGAP’s GAP activity is necessary early during cytokinesis for the formation and maintenance of the Rho activity zone. Disruption of GAP activity by point mutation results in poorly focused Rho activity zones, while complete removal of the GAP domain results in unfocused zones that display lateral instability and/or rapid side-to-side oscillations. We propose that the GAP domain of MgcRacGAP plays two unexpected roles throughout cytokinesis: first, it transiently anchors active Rho, and second it promotes local Rho inactivation resulting in the constant flux of Rho through the GTPase cycle.
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)。
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