cua-1;daf-2

CU (copper) ATPase

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Locus: CELE_Y76A2A.2

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Wormbase description: cua-1 encodes a copper-transporting E1-E2 ATPase orthologous to the human gene ATP7A (OMIM:604384), which when mutated leads to Hailey-Hailey disease; loss of cua-1 activity via RNAi results in a number of defects, including slow growth, uncoordinated or no locomotion, adult and larval lethality, and axon guidance abnormalities; when overexpressed in S. cerevisiae ccc2 mutants, a cua-1 cDNA is able to complement observed defects suggesting that, in vivo, CUA-1 functions as a copper transporter; in C. elegans, a cua-1::GFP promoter fusion is strongly expressed in the adult intestine, with particularly strong expression in the anterior intestine, and highly expressed in the hypodermal cells of the head and body regions in the L1 larval stage; in addition, the cua-1::GFP fusion is also expressed in muscles in the pharyngeal terminal bulb; cua-1::GFP expression is not seen in the intestine of dauer larvae.

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Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

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Locus: CELE_Y55D5A.5

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Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

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