Lifespan changes: From wild type to ain-1;daf-2 / From ain-1;daf-2 to multiple mutants
Fifty-seven gene inactivations (corresponding to 55 RNAi clones) more dramatically shortened the life span of daf-2 animals compared with daf-2;daf-16, but still shortened the life span of daf-2;daf-16 animals, suggesting that they function in a parallel/converging pathway to insulin/IGF1 signaling
Double mutant ain-1(RNAi);daf-2(e1370) has a lifespan of 31.1 days, while single mutant daf-2(e1370) has a lifespan of 36.7 days and wild type has a lifespan of 14.7 days.
Samuelson AV et al., 2007, Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev. 21(22):2976-94 18006689 Click here to select all mutants from this PubMed ID in the graph
ALG-1 INteracting protein
Wormbase description: ain-1 encodes an unfamiliar protein synergistically required, with LIN-31, for the normal timing of vulval differentiation, independently of LET-60/RAS, and parallel to or downstream of LIN-14/LIN-28/HBL-1; AIN-1 is expressed in cytoplasmic foci (that are probably P bodies) in several tissues, including vulval precursor cells and neurons; AIN-1 coimmunoprecipitates with DCR-1 and ALG-1, also binds ALG-1 in vitro, and does not require DNA or RNA for its binding; in vivo, AIN-1 targets ALG-1 to cytoplasmic foci, in which it colocalizes with DCAP-2; AIN-1 is likely to be a RISC component, since anti-AIN-1 antibodies precipitate 29 different miRNAs, including mir-2, mir-52, mir-58, mir-71, mir-77, and mir-239a; ain-1(ku322) mutants are essentially wild-type, except for sporadically gapped alae and excess seam cell nuclei arising from retarded seam cell fusion; more prominently, ain-1(ku322) suppresses the multivulva phenotype of lin-31(n1053) mutations, while strongly enhancing lin-31(n1053)'s egg-laying defect; the cellular basis of lin-31(n1053);ain-1(ku322) phenotypes is a delay in vulval development in L4 larvae not seen with either mutation alone; ain-1(ku322) has no effect on let-60(n1046) or lin-3(e1275) mutations; ain-1(ku322) suppresses the precocious vulval development of lin-14(RNAi), lin-28 mutants, and hbl-1(RNAi); alg-1 or alg-1 ain-1 mutant alae resemble ain-1 alae, indicating that ALG-1 and AIN-1 act in a common genetic pathway; AIN-1 is homologous to Brugia malayi 14748.m00068, 14052.m00191, and 14963.m01790, and paralogous to C. elegans B0041.2; AIN-1 and its nematode homologs have weak similarity to human TNRC6A (GW182; OMIM:610739) and Drosophila GAWKY.
Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein
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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