Lissemore J L, Currie P D, Turk C M, Maine E M
Department of Biology, Syracuse University, New York 13244-1270.
Genetics. 1993 Dec;135(4):1023-34. doi: 10.1093/genetics/135.4.1023.
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.
在秀丽隐杆线虫发育过程中，glp - 1基因产物介导细胞命运决定所需的细胞间相互作用。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型glp - 1等位基因的显性抑制子，并获得了18个抑制生殖系和胚胎glp - 1表型的突变。这些显性抑制子与glp - 1紧密连锁，且不绕过对远端末梢细胞的需求，远端末梢细胞被认为是GLP - 1蛋白接收和转导信号的来源。通过单链构象多态性（SSCP）分析和DNA测序，我们发现至少17个抑制子是第二位点基因内回复突变体。这些抑制子与最初的glp - 1（ts）突变一样，都位于GLP - 1的cdc10/SWI6/锚蛋白结构域。已证明cdc10/SWI6/锚蛋白基序在其他多肽中介导特定的蛋白质 - 蛋白质相互作用。我们提出，glp - 1（ts）突变破坏了GLP - 1与尚未鉴定的靶蛋白之间的接触，而显性抑制子突变恢复了适当的蛋白质 - 蛋白质相互作用。
