Intragenic dominant suppressors of glp-1, a gene essential for cell-signaling in Caenorhabditis elegans, support a role for cdc10/SWI6/ankyrin motifs in GLP-1 function.

Intragenic dominant suppressors of glp-1, a gene essential for cell-signaling in Caenorhabditis elegans, support a role for cdc10/SWI6/ankyrin motifs in GLP-1 function.
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glp-1(一种对秀丽隐杆线虫细胞信号转导至关重要的基因)的基因内显性抑制因子支持 cdc10/SWI6/锚蛋白基序在 GLP-1 功能中的作用。

DOI:
10.1093/genetics/135.4.1023
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发表时间:
1993
期刊:
影响因子:
3.3
通讯作者:
Maine,EM
Maine,EM
中科院分区:
生物学2区
文献类型:
--
作者:
Lissemore,JL;Currie,PD;Turk,CM;Maine,EM

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GLP-1基因产物介导秀丽隐杆线虫发育过程中细胞命运规范所需的细胞-细胞相互作用。为了鉴定与glp-1相互作用的基因,我们筛选了两个温度敏感的glp-1等位基因的显性抑制基因,并回收了18个抑制生殖系和胚胎glp-1表型的突变。这些显性抑制因子与GLP-1紧密相连,并且不能绕过对远端细胞的需求,远端细胞被认为是GLP-1蛋白接收和转导的信号来源。利用单链构象多态性(SSCP)分析和DNA测序,我们发现至少有17个抑制子是第二位点基因内回复突变体。与原始glp-1(ts)突变一样,抑制因子均位于GLP-1的cdc 10/SWI 6/锚蛋白结构域中。cdc 10/SWI 6/锚蛋白基序已显示在其它多肽中介导特异性蛋白质-蛋白质相互作用。我们认为glp-1(ts)突变破坏了GLP-1与尚未鉴定的靶蛋白之间的接触,而显性抑制突变恢复了适当的蛋白质-蛋白质相互作用。
The glp-1 gene product mediates cell-cell interactions required for cell fate specification during development in Caenorhabditis elegans. To identify genes that interact with glp-1, we screened for dominant suppressors of two temperature-sensitive glp-1 alleles and recovered 18 mutations that suppress both germline and embryonic glp-1 phenotypes. These dominant suppressors are tightly linked to glp-1 and do not bypass the requirement for a distal tip cell, which is thought to be the source of a signal that is received and transduced by the GLP-1 protein. Using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, we found that at least 17 suppressors are second-site intragenic revertants. The suppressors, like the original glp-1(ts) mutations, are all located in the cdc10/SWI6/ankyrin domain of GLP-1. cdc10/SWI6/ankyrin motifs have been shown to mediate specific protein-protein interactions in other polypeptides. We propose that the glp-1(ts) mutations disrupt contact between GLP-1 and an as yet unidentified target protein(s) and that the dominant suppressor mutations restore appropriate protein-protein interactions.
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