Antagonism between Goα and Gqα in Caenorhabditis elegans:: the RGS protein EAT-16 is necessary for Goα signaling and regulates Gqα activity
Antagonism between Goα and Gqα in Caenorhabditis elegans:: the RGS protein EAT-16 is necessary for Goα signaling and regulates Gqα activity
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DOI：
10.1101/gad.13.14.1780
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发表时间：
1999-07-15
影响因子：
10.5
通讯作者：
Sternberg, PW
中科院分区：
文献类型：
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作者：
Hajdu-Cronin, YM;Chen, WJ;Sternberg, PW
为了阐明异三聚体G蛋白G(O)在细胞中的作用，我们对秀丽隐杆线虫进行了分子遗传学研究。我们筛选了激活的GoA-1(G(O)Alpha)的抑制子，发现只有两个基因发生突变，即sag-1和Eat-16。任何一种基因缺陷的动物都表现出类似于GOA-1功能丧失突变体的过度活跃表型。双突变分析表明，SAG-1和EAT-16都作用于G(O)α下游或平行于G(O)α，负调控EGL-30(G(Q)α)信号。EAT-16编码一种类似于哺乳动物RGS7和RGS9蛋白的G蛋白信号转导调节因子，能抑制COS-7细胞内源性G(Q)/G(11)。同时缺失sag-1和Eat-16的动物是不能存活的，但eg1-30的功能降低可以恢复存活能力，这表明Eat-16；sag-1双突变体的致命性是由于G(Q)α活性过高所致。对这些突变的分析表明，G(O)和G(Q)通路在线虫中的作用是拮抗的，而G(O)α。负调控G(Q)途径，可能通过EAT-16或SAG-1。我们认为G(O)的主要细胞作用是拮抗G(Q)所传递的信号。
To elucidate the cellular role of the heterotrimeric G protein G(o), we have taken a molecular genetic approach in Caenorhabditis elegans. We screened for suppressors of activated GOA-1 (G(o)alpha) that do not simply decrease its expression and found mutations in only two genes, sag-1 and eat-16. Animals defective in either gene display a hyperactive phenotype similar to that of goa-1 loss-of-function mutants. Double-mutant analysis indicates that both sag-1 and eat-16 act downstream of, or parallel to, G(o)alpha and negatively regulate EGL-30 (G(q)alpha) signaling. eat-16 encodes a regulator of G protein signaling (RGS) most similar to the mammalian RGS7 and RGS9 proteins and can inhibit endogenous mammalian G(q)/G(11) in COS-7 cells. Animals defective in both sag-1 and eat-16 are inviable, but reducing function in eg1-30 restores viability, indicating that the lethality of the eat-16; sag-1 double mutant is due to excessive G(q)alpha activity. Analysis of these mutations indicates that the G(o) and G(q) pathways function antagonistically in C. elegans, and that G(o)alpha. negatively regulates the G(q) pathway, possibly via EAT-16 or SAG-1. We propose that a major cellular role of G(o) is to antagonize signaling by G(q).