Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans.
The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development. The glp-1 product is required for induction of germ-line proliferation and for embryogenesis. By contrast, lin-12 mediates somatic cell interactions, including those between the precursor cells that form the vulval hypodermis (VPCs). Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality). We find that the effects of glp-1(q35) on VPC development mimic those of dominant lin-12 mutations, even in the absence of lin-12 activity. The glp-1(q35) gene bears a nonsense mutation predicted to eliminate the 122 C-terminal amino acids, including a ProGluSerThr (PEST) sequence thought to destabilize proteins. We suggest that the carboxy terminus bears a negative regulatory domain which normally inactivates glp-1 in the VPCs. We propose that inappropriate glp-1(q35) activity can substitute for lin-12 to determine vulval fate, perhaps by driving the VPCs to proliferate.
Mango
S E
SE
Department of Biochemistry, University of Wisconsin-Madison 53706.
Maine
E M
EM
Kimble
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002107:Caenorhabditis / Q000196:embryology / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division; D005260:Female; D005854:Germ Cells / Q000166:cytology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D051880:Receptors, Notch; D014844:Vulva / Q000196:embryology / Q000254:growth & development
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051880:Receptors, Notch