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.
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.
Lissemore
J L
JL
Department of Biology, Syracuse University, New York 13244-1270.
Currie
P D
PD
Turk
C M
CM
Maine
E M
EM
D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D029742:Caenorhabditis elegans Proteins; D002450:Cell Communication / Q000235:genetics*; D005787:Gene Frequency; D005799:Genes, Dominant; D017238:Genes, Helminth; D016153:Genes, Suppressor; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D015801:Helminth Proteins; D008562:Membrane Glycoproteins; D051880:Receptors, Notch