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Gene Review

nct  -  nicastrin

Drosophila melanogaster

Synonyms: CG7012, Dmel\CG7012, NCSTN, Nct, Nic, ...
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Disease relevance of nct


High impact information on nct

  • Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion [2].
  • The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin [3].
  • Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex [4].
  • Our results indicate that the four components of gamma-secretase, viz. presenilin, nicastrin, APH-1, and PEN-2, are present and enriched on phagosome membranes from both murine macrophages and Drosophila S2 phagocytes [5].
  • In addition, we show that Nicastrin as well as Notch are required to maintain normal R-cell morphology, because the nuclei of mutant photoreceptor neurons cannot maintain their proper position [1].

Biological context of nct


Anatomical context of nct


Physical interactions of nct

  • Aph-1 and Nct may form a subcomplex that stabilizes the Psn holoprotein at an early step in gamma-secretase assembly [4].

Regulatory relationships of nct

  • Further, Nicastrin is genetically required for signaling from membrane-anchored activated Notch [6].

Other interactions of nct

  • Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step [8].
  • Nicastrin might recruit gamma-secretase substrates into the proteolytic complex as a prerequisite for Presenilin maturation and active complex assembly [6].


  1. Nicastrin controls aspects of photoreceptor neuron specification and differentiation in the Drosophila eye. Zhang, T., Tran, S., Clouser, C., Pignoni, F. Dev. Dyn. (2005) [Pubmed]
  2. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y.Q., Rogaeva, E., Chen, F., Kawarai, T., Supala, A., Levesque, L., Yu, H., Yang, D.S., Holmes, E., Milman, P., Liang, Y., Zhang, D.M., Xu, D.H., Sato, C., Rogaev, E., Smith, M., Janus, C., Zhang, Y., Aebersold, R., Farrer, L.S., Sorbi, S., Bruni, A., Fraser, P., St George-Hyslop, P. Nature (2000) [Pubmed]
  3. Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. Chung, H.M., Struhl, G. Nat. Cell Biol. (2001) [Pubmed]
  4. Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. Hu, Y., Fortini, M.E. J. Cell Biol. (2003) [Pubmed]
  5. Gamma-secretase is a functional component of phagosomes. Jutras, I., Laplante, A., Boulais, J., Brunet, S., Thinakaran, G., Desjardins, M. J. Biol. Chem. (2005) [Pubmed]
  6. Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor. Hu, Y., Ye, Y., Fortini, M.E. Dev. Cell (2002) [Pubmed]
  7. Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions. Niimura, M., Isoo, N., Takasugi, N., Tsuruoka, M., Ui-Tei, K., Saigo, K., Morohashi, Y., Tomita, T., Iwatsubo, T. J. Biol. Chem. (2005) [Pubmed]
  8. Drosophila nicastrin is essential for the intramembranous cleavage of notch. López-Schier, H., St Johnston, D. Dev. Cell (2002) [Pubmed]
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