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Gene Review

sel-12  -  Protein SEL-12

Caenorhabditis elegans

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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


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].


  1. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Levitan, D., Greenwald, I. Nature (1995) [Pubmed]
  2. 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. Jarriault, S., Greenwald, I. Genes Dev. (2002) [Pubmed]
  3. Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1. Eimer, S., Lakowski, B., Donhauser, R., Baumeister, R. EMBO J. (2002) [Pubmed]
  4. 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. Wen, C., Levitan, D., Li, X., Greenwald, I. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling. Westlund, B., Parry, D., Clover, R., Basson, M., Johnson, C.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. The Caenorhabditis elegans presenilin sel-12 is required for mesodermal patterning and muscle function. Eimer, S., Donhauser, R., Baumeister, R. Dev. Biol. (2002) [Pubmed]
  7. Effects of SEL-12 presenilin on LIN-12 localization and function in Caenorhabditis elegans. Levitan, D., Greenwald, I. Development (1998) [Pubmed]
  8. The role of the presenilin-1 homologue gene sel-12 of Caenorhabditis elegans in apoptotic activities. Kitagawa, N., Shimohama, S., Oeda, T., Uemura, K., Kohno, R., Kuzuya, A., Shibasaki, H., Ishii, N. J. Biol. Chem. (2003) [Pubmed]
  9. APH-2/nicastrin functions in LIN-12/Notch signaling in the Caenorhabditis elegans somatic gonad. Levitan, D., Yu, G., St George Hyslop, P., Goutte, C. Dev. Biol. (2001) [Pubmed]
  10. The presenilins and Alzheimer's disease. Hutton, M., Hardy, J. Hum. Mol. Genet. (1997) [Pubmed]
  11. Human presenilin-1, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing. Baumeister, R., Leimer, U., Zweckbronner, I., Jakubek, C., Grünberg, J., Haass, C. Genes Funct. (1997) [Pubmed]
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