Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis

Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis
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DOI:
10.1083/jcb.137.4.891
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发表时间:
1997-05-19
影响因子:
7.8
通讯作者:
Sutoh, K
Sutoh, K
中科院分区:
生物学1区
文献类型:
--
作者:
Adachi, H;Takahashi, Y;Sutoh, K

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gapA基因编码一种新的RasGTP酶激活蛋白(RasGAP)相关的蛋白被发现被破坏的胞质分裂突变体的Dictyosteoblastoma生长的巨大和多核细胞在培养皿中。GAPA蛋白的预测序列与来自裂殖酵母的Gap 1/Sar 1和哺乳动物IQGAP的COOH末端的一半显示出相当大的同源性,这种相似性延伸到RasGAP相关结构域之外。在悬浮培养中,gapA(-)细胞显示正常生长,细胞质量增加,但胞质分裂无效,产生球形巨细胞。对培养皿中细胞分裂动力学的延时记录显示,在gapA(-)细胞的情况下,胞质分裂在连接子细胞的中间体应该被切断的步骤中经常被逆转。gapA(-)细胞胞质分裂的早期步骤似乎是正常的,因为肌球蛋白II积累在卵裂沟。饥饿时,gnpA(-)细胞发育并形成具有活孢子的子实体,就像野生型细胞一样。这些结果表明GAPA蛋白特异性地参与胞质分裂的完成。最近,据报道,IQGAP是推定的Rac和CDC 42,GTP酶的Rho家族成员的效应器,并参与肌动蛋白细胞骨架的重组。因此,这是可能的,网骨藻GAPA参与切断的中体通过调节肌动蛋白细胞骨架通过与小GTP酶的成员的相互作用。
The gapA gene encoding a novel RasGTPase-activating protein (RasGAP)-related protein was found to be disrupted in a cytokinesis mutant of Dictyostelium that grows as giant and multinucleate cells in a dish culture. The predicted sequence of the GAPA protein showed considerable homology to those of Gap1/Sar1 from fission yeast and the COOH-terminal half of mammalian IQGAPs, the similarity extending beyond the RasGAP-related domain. In suspension culture, gapA(-) cells showed normal growth in terms of the increase in cell mass, but cytokinesis inefficiently occurred to produce spherical giant cells. Time-lapse recording of the dynamics of cell division in a dish culture revealed that, in the case of gapA(-) cells, cytokinesis was very frequently reversed at the step in which the midbody connecting the daughter cells should be severed. Earlier steps of cytokinesis in the gapA(-) cells seemed to be normal, since myosin II was accumulated at the cleavage furrow. Upon starvation, gnpA(-) cells developed and formed fruiting bodies with viable spores, like the wild-type cells. These results indicate that the GAPA protein is specifically involved in the completion of cytokinesis. Recently, it was reported that IQGAPs are putative effecters for Rac and CDC42, members of the Rho family of GTPases, and participate in reorganization of the actin cytoskeleton. Thus, it is possible that Dictyostelium GAPA participates in the severing of the midbody by regulating the actin cytoskeleton through an interaction with a member of small GTPases.