Psychiatry related information on sel-12

• The sel-12 gene encodes a protein with multiple transmembrane domains, and is similar to S182, which has been implicated in early-onset familial Alzheimer's disease [1].

High impact information on sel-12

• Suppressors of the egg-laying defective phenotype of sel-12 presenilin mutants implicate the CoREST corepressor complex in LIN-12/Notch signaling in C. elegans [2].
• In Caenorhabditis elegans, mutations in the presenilin sel-12 result in a highly penetrant egg-laying defect. spr-5 was identified as an extragenic suppressor of the sel-12 mutant phenotype [3].
• Moreover, down-regulation of SPR-1 by mutation or RNA interference also bypasses the need for sel-12 [3].
• spr-2, a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans, is a member of the SET protein subfamily [4].
• Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion [5].

Biological context of sel-12

• Together with a previous study indicating a role of lin-12 and sel-12 during the specification of the pi cell lineage required for proper vulva-uterine connection, our data suggest that the failure of sel-12 animals to lay eggs properly is caused by defects in at least two independent signalling events in different tissues during development [6].
• Reducing sel-12 activity can suppress the effects of elevated lin-12 activity when LIN-12 is activated by missense mutations but not when LIN-12 is activated by removal of the extracellular and transmembrane domains [7].
• In this study, we examined the role of the PS1 homologue gene sel-12 of Caenorhabditis elegans under oxidative stress and clarified the sel-12-induced apoptosis [8].
• We show here that a reduction of the activity of the Caenorhabditis elegans presenilin sel-12 results in a late defect during sex muscle development [6].

Anatomical context of sel-12

• Both weak and strong sel-12 mutations cause defects in the sex muscles that resemble the defects we found in lin-12 hypomorphic alleles, suggesting a previously uncharacterised LIN-12 signalling event late in postembryonic mesoderm development [6].
• An active SEL-12::GFP hybrid protein accumulates in the perinuclear region of the vulval precursor cells (VPCs) of living hermaphrodites, consistent with a localization in endoplasmic reticulum/Golgi membranes; when sel-12 activity is reduced, less LIN-12 protein accumulates in the plasma membranes of the VPCs [7].
• We also show that aph-2 and sel-12 genetically interact and cooperate to regulate LIN-12/Notch signaling in the development of the somatic gonad [9].

Other interactions of sel-12

• Both defects can be rescued by expressing sel-12 from the hlh-8 promoter that is active during the development of the sex muscle-specific M lineage, but not by expressing sel-12 from late muscle-specific promoters [6].
• Work on the Caenorhabditis elegans homologues of the presenilins, spe-4 and sel-12, suggests that the presenilins may have a more general and direct role in the processing and trafficking of membrane-bound proteins and that, in part, the pathogenic mutations may disrupt this role [10].
• These genes show considerable sequence similarity to the sel-12 gene of Caenorhabditis elegans, which has been postulated to function in the facilitated signalling by lin-12 and glp-1 [11].

References