Evidence for functional redundancy between C. elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE.
The ectodomain of LIN-12/Notch proteins is cleaved and shed upon ligand binding. In Caenorhabditis elegans, genetic evidence has implicated SUP-17, the ortholog of Drosophila Kuzbanian and mammalian ADAM10, as the protease that mediates this event. In mammals, however, biochemical evidence has implicated TACE, a different ADAM protein. We have investigated potential functional redundancy of sup-17 and the C. elegans ortholog of TACE, adm-4, by exploring their roles in cell fate decisions mediated by lin-12/Notch genes. We found that reduced adm-4 activity, like reduced sup-17 activity, suppresses an allele of glp-1 that encodes a constitutively active receptor. Furthermore, concomitant reduction of adm-4 and sup-17 activity causes the production of two anchor cells in the hermaphrodite gonad, instead of one--a phenotype associated with loss of lin-12 activity. Concomitant reduction of both sup-17 and adm-4 activity in hermaphrodites results in highly penetrant synthetic sterility, which appears to reflect a defect in the spermatheca. Expression of a truncated form of LIN-12 that mimics the product of ectodomain shedding rescues this fertility defect, suggesting that sup-17 and adm-4 may mediate ectodomain shedding of LIN-12 and/or GLP-1. Our results are consistent with the possibility that sup-17 and adm-4 are functionally redundant for at least a subset of LIN-12/Notch-mediated decisions in C. elegans.
Jarriault
Sophie
S
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Greenwald
Iva
I
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000072198:ADAM17 Protein; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009865:Oocytes / Q000502:physiology; D010802:Phylogeny; D051880:Receptors, Notch / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics; D015032:Zinc / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; C082460:Lin-12 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D051722:ADAM Proteins; D008666:Metalloendopeptidases; C109978:SUP-17 protein, C elegans; D000072198:ADAM17 Protein; D015032:Zinc