Control of embryonic spindle positoning and Gα activity by C-elegans RIC-8

被引:77
作者
Couwenbergs, C [1 ]
Spilker, AC [1 ]
Gotta, M [1 ]
机构
[1] ETH, Inst Biochem, CH-8093 Zurich, Switzerland
关键词
D O I
10.1016/j.cub.2004.09.059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Asymmetric spindle positioning is of fundamental importance for generating cell diversity during development. In the C. elegans 1 cell embryo, spindle positioning has been shown to depend on heterotrimeric G protein signaling. Two Galpha subunits, GOA-1 and GPA-16 (hereafter Galpha), and receptor independent activators of G protein signaling GPR-1 and GPR-2 (GPR1/2) are required for proper regulation of spindle positioning [1]. However, it remains unclear whether Galpha regulates spindle positioning in its GDP or GTP bound form. Here, we investigate the role of RIC-8 in this pathway. RIC-8 was genetically shown to act in concert with goa-1 to regulate centrosome movements in C. elegans [2, 3]. Interestingly, mammalian RIC-8 was recently found to behave as a GEF for Galpha subunits in vitro [4]. We show that reduction of function of ric-8 results in a 1 cell embryo phenotype very similar to the phenotype of embryos depleted of Galpha. RIC-8 is able to directly bind to GOA-1, preferentially to GOA-1-GDP, consistent with a GEF role. RIC-8 is localized at the embryo cortex, and its activity is essential for the asymmetric localization of GPR-1/2. We suggest that RIC-8 directly modulates Galpha activity and that Galpha-GTP is the signaling molecule regulating spindle positioning in the early embryo.
引用
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页码:1871 / 1876
页数:6
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