daf-16;glp-1;nhr-80

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Protein glp-1

Locus: CELE_F02A9.6

Wormbase description: glp-1 encodes an N-glycosylated transmembrane protein that, along with LIN-12, comprises one of two C. elegans members of the LIN-12/Notch family of receptors; from the N- to the C-terminus, GLP-1 is characterized by ten extracellular EGF-like repeats, three LIN-12/Notch repeats, a CC-linker, a transmembrane domain, a RAM domain, six intracellular ankyrin repeats, and a PEST sequence; in C. elegans, GLP-1 activity is required for cell fate specification in germline and somatic tissues; in the germline, GLP-1, acting as a receptor for the DSL family ligand LAG-2, is essential for mitotic proliferation of germ cells and maintenance of germline stem cells; in somatic tissues, maternally provided GLP-1, acting as a receptor for the DSL family ligand APX-1, is required for inductive interactions that specify the fates of certain embryonic blastomeres; GLP-1 is also required for some later embryonic cell fate decisions, and in these decisions its activity is functionally redundant with that of LIN-12; GLP-1 expression is regulated temporally and spatially via translational control, as GLP-1 mRNA, present ubiquitously in the germline and embryo, yields detectable protein solely in lateral, interior, and endomembranes of distal, mitotic germ cells, and then predominantly in the AB blastomere and its descendants in the early embryo; proper spatial translation of glp-1 mRNA in the embryo is dependent upon genes such as the par genes, that are required for normal anterior-posterior asymmetry in the early embryo; signaling through GLP-1 controls the activity of the downstream Notch pathway components LAG-3 and LAG-1, the latter being predicted to function as part of a transcriptional feedback mechanism that positively regulates GLP-1 expression; signaling through the DNA-binding protein LAG-1 is believed to involve a direct interaction between LAG-1 and the GLP-1 RAM and ankyrin domains

Nuclear Hormone Receptor family

Locus: CELE_H10E21.3

Wormbase description: nhr-80 encodes a nuclear hormone receptor, expressed in the intestine, that regulates expression of the delta-9 desaturases FAT-5/-6/-7, and thus regulates fatty acid metabolism; NHR-80 is fully required for any expression of FAT-7, full expression of FAT-5/-6, viability in the absence of FAT-6, and transcriptional hyperactivation of fat-7 in the absence of FAT-6, and for a fully normal adult lifespan; nhr-80 is expressed robustly in the intestine during larval and adult stages of development, with some expression also seen in head muscles; nhr-80 is specific to nematodes, being a divergent ortholog of HNF4 with many paralogs in C. elegans; nhr-80(tm1011) mutants, like nhr-49 mutants, have an increased ration of saturated 18:0 fatty acids to monounsaturated 18:1 ones (4.6 instead of 2.2); nhr-80(tm1011) mutants are viable and fertile and have no increase in fat storage, but double fat-6(tm331);nhr-80(tm1011) mutants, (or fat-6(tm331) mutants subjected to nhr-80(RNAi), are synthetically lethal unless cultured on media supplemented with desaturated fatty acids.