RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans
RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans
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DOI：
10.1038/sj.emboj.7601922
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Zwartkruis, Fried J. T.
中科院分区：
文献类型：
--
作者：
Frische, Ester W.;Pellis-van Berkel, Wendy;Zwartkruis, Fried J. T.
小Ras样GTIP 1 Rap 1已被鉴定为整合素活化和钙粘蛋白介导的细胞-细胞接触的调节因子。令人惊讶的是，在秀丽隐杆线虫中RAP-1的无效突变体是可行的和可育的。在用C.在elegans rap-31突变体中，Ras样GTcirral-1作为生存力特异性所需的七个基因之一出现。耗尽exoc-8和sec-5，编码两个推定的RAL-1效应器和外囊复合物的成员，也引起rap-1突变体的致死性，但不影响野生型蠕虫。RAP-1和RAL-1/exocyst途径似乎在胚胎发育过程中协调皮下细胞的运动和伸长。它们部分通过将α-连环蛋白同源物HMP-1靶向至侧膜来介导其作用。遗传相互作用表明，RAP-1和RAL-1/exocyst途径在幼虫阶段也平行发挥作用。这些数据一起提供了外囊复合物作为细胞迁移中的下游RAL-1效应物的体内证据。
The small Ras-like GTPase Rap1 has been identified as a regulator of integrin activation and cadherin-mediated cell-cell contacts. Surprisingly, null mutants of RAP-1 in Caenorhabditis elegans are viable and fertile. In a synthetic lethal RNAi screen with C. elegans rap-31 mutants, the Ras-like GTPase ral-1 emerged as one of seven genes specifically required for viability. Depletion of exoc-8 and sec-5, encoding two putative RAL-1 effectors and members of the exocyst complex, also caused lethality of rap-1 mutants, but did not affect wild-type worms. The RAP-1 and the RAL-1/exocyst pathway appear to coordinate hypodermal cell movement and elongation during embryonic development. They mediate their effect in part through targeting the alpha-catenin homologue HMP-1 to the lateral membrane. Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration.