SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling.
LIN-12/NOTCH proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
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Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Metzstein
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Greenwald
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D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D017124:Conserved Sequence; D019483:Disintegrins / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D051880:Receptors, Notch; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D019483:Disintegrins; D029721:Drosophila Proteins; D015801:Helminth Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; C100953:KUZ protein, Drosophila; D008666:Metalloendopeptidases; C109978:SUP-17 protein, C elegans; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human