Localization of Giα proteins in the centrosomes and at the midbody:: implication for their role in cell division

Localization of Giα proteins in the centrosomes and at the midbody:: implication for their role in cell division
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DOI:
10.1083/jcb.200604114
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发表时间:
2007-07-16
影响因子:
7.8
通讯作者:
Kehrl, John H.
Kehrl, John H.
中科院分区:
生物学1区
文献类型:
--
作者:
Cho, Hyeseon;Kehrl, John H.

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在质膜上,异三聚体G蛋白作为分子开关,传递来自G蛋白偶联受体的信号;然而,G(α)亚基在细胞内也具有与受体无关的功能。G蛋白信号传导调节因子(RGS) 14可增强G(i α)蛋白的内在GTPase活性,其定位于中心体,提示G(i α)的共表达。我们显示了G(i α 1), G(i α 2)和G(i α 3)在中心体和中间体中的表达。荧光共振能量转移分析证实了RGS14与中心体中G(i α 1)的直接相互作用。gtpase缺陷型G(i α 1)的表达导致细胞分裂缺陷,而野生型或gtpase缺陷型G(i α 3)的表达导致有丝分裂延长。经百日咳毒素处理的细胞,G(i α 1)、G(i α 2)和G(i α 3)表达减少或RGS14表达减少也表现出细胞分裂缺陷。这些结果表明,G(i α)蛋白及其在这些位点的调节因子可能在哺乳动物细胞分裂过程中起重要作用。
At the plasma membrane, heterotrimeric G proteins act as molecular switches to relay signals from G protein-coupled receptors; however, G(alpha) subunits also have receptor-independent functions at intracellular sites. Regulator of G protein signaling (RGS) 14, which enhances the intrinsic GTPase activity of G(i alpha) proteins, localizes in centrosomes, which suggests the coexpression of G(i alpha). We show expression of G(i alpha 1), G(i alpha 2), and G(i alpha 3) in the centrosomes and at the midbody. Fluorescence resonance energy transfer analysis confirms a direct interaction between RGS14 and G(i alpha 1) in centrosomes. Expression of GTPase-deficient G(i alpha 1) results in defective cytokinesis, whereas that of wild-type or GTPase-deficient G(i alpha 3) causes prolonged mitosis. Cells treated with pertussis toxin, with reduced expression of G(i alpha 1), G(i alpha 2), and G(i alpha 3) or with decreased expression of RGS14 also exhibit cytokinesis defects. These results suggest that G(i alpha) proteins and their regulators at these sites may play essential roles during mammalian cell division.