Gene Symbol: nct
Description: nicastrin
Alias: CG7012, Dmel\CG7012, Nct, Nic, S5A, ST96B, agro, dNct, nic, nicastrin, CG7012-PA, CG7012-PC, CG7012-PD, CG7012-PE, agoraphobic, dNicastrin, nct-PA, nct-PC, nct-PD, nct-PE
Species: fruit fly

Top Publications

  1. Hu Y, Ye Y, Fortini M. Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor. Dev Cell. 2002;2:69-78 pubmed
    b>Nicastrin is genetically linked to Notch/lin-12 signaling in C. elegans and is part of a large multiprotein complex along with Presenilin. Here we describe the isolation and characterization of Drosophila Nicastrin (Nic) mutants...
  2. Chung H, Struhl G. Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. Nat Cell Biol. 2001;3:1129-32 pubmed
    The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin...
  3. Lopez Schier H, St Johnston D. Drosophila nicastrin is essential for the intramembranous cleavage of notch. Dev Cell. 2002;2:79-89 pubmed
    ..Presenilin is found in a multisubunit complex that also contains Nicastrin. Nicastrin has been implicated in APP processing, but its role in Notch signaling remains unclear...
  4. Francis R, McGrath G, Zhang J, Ruddy D, Sym M, Apfeld J, et al. aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell. 2002;3:85-97 pubmed
    ..and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin. Human aph-1 and pen-2 partially rescue the C. elegans mutant phenotypes, demonstrating conserved functions...
  5. Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, Takahashi Y, et al. The role of presenilin cofactors in the gamma-secretase complex. Nature. 2003;422:438-41 pubmed
    ..that, in addition to the endoproteolysed fragmented form of presenilin, contains essential cofactors including nicastrin, APH-1 (refs 15-18) and PEN-2 (refs 16, 19)...
  6. Guo M, Hong E, Fernandes J, Zipursky S, Hay B. A reporter for amyloid precursor protein gamma-secretase activity in Drosophila. Hum Mol Genet. 2003;12:2669-78 pubmed
    ..gamma-Secretase resides in a large multi-protein complex, of which Presenilin, Nicastrin, APH-1 and PEN-2 are four essential components...
  7. Loewer A, Soba P, Beyreuther K, Paro R, Merdes G. Cell-type-specific processing of the amyloid precursor protein by Presenilin during Drosophila development. EMBO Rep. 2004;5:405-11 pubmed
    ..Using this system, we demonstrate differences between APP and Notch processing and show that PS-mediated cleavage of APP can be regulated in different cell types independent of the size of the extracellular domain. ..
  8. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, et al. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature. 2000;407:48-54 pubmed
    b>Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2...
  9. Hu Y, Fortini M. Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol. 2003;161:685-90 pubmed
    ..Four putative gamma-secretase components have been identified-presenilin (Psn), nicastrin (Nct), Aph-1, and Pen-2...

More Information


  1. Kopan R, Goate A. Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization. Neuron. 2002;33:321-4 pubmed
    ..The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP...
  2. Troost T, Schneider M, Klein T. A re-examination of the selection of the sensory organ precursor of the bristle sensilla of Drosophila melanogaster. PLoS Genet. 2015;11:e1004911 pubmed publisher
    ..These results suggest that the tissue specific proneural proteins of Drosophila have a similar function as in the vertebrates, which is to determine the time of emergence and position of the SOP and to stabilise the proneural state. ..
  3. Isoo N, Sato C, Miyashita H, Shinohara M, Takasugi N, Morohashi Y, et al. Abeta42 overproduction associated with structural changes in the catalytic pore of gamma-secretase: common effects of Pen-2 N-terminal elongation and fenofibrate. J Biol Chem. 2007;282:12388-96 pubmed
    ..gamma-Secretase is a multimeric membrane protein complex composed of presenilin (PS), nicastrin, Aph-1, and Pen-2...
  4. Zhang T, Tran S, Clouser C, Pignoni F. Nicastrin controls aspects of photoreceptor neuron specification and differentiation in the Drosophila eye. Dev Dyn. 2005;234:590-601 pubmed
    b>Nicastrin is a component of the Notch signaling pathway involved in proteolytic release of the Notch receptor intracellular domain...
  5. Kang J, Shin S, Perrimon N, Shen J. An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain. Genetics. 2017;206:1479-1493 pubmed publisher
    Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of ?-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins...
  6. van de Hoef D, Bonner J, Boulianne G. FKBP14 is an essential gene that regulates Presenilin protein levels and Notch signaling in Drosophila. Development. 2013;140:810-9 pubmed publisher
    ..Altogether, our data demonstrate that FKBP14 plays an essential role in development, one aspect of which includes regulating members of the Notch signaling pathway. ..
  7. Stempfle D, Kanwar R, Loewer A, Fortini M, Merdes G. In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity. Mol Cell Biol. 2010;30:3165-75 pubmed publisher
    ..based on expression of epitope-tagged versions of the four core gamma-secretase components, Presenilin, Nicastrin, Aph-1, and Pen-2...
  8. Gross G, Feldman R, Ganguly A, Wang J, Yu H, Guo M. Role of X11 and ubiquilin as in vivo regulators of the amyloid precursor protein in Drosophila. PLoS ONE. 2008;3:e2495 pubmed publisher
    ..Since increased expression of X11 attenuates Abeta production and/or secretion in APP transgenic mice, but does not act on gamma-secretase directly, X11 may represent an attractive therapeutic target for AD. ..
  9. Vied C, Kalderon D. Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind. Development. 2009;136:2177-86 pubmed publisher
    ..Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary. ..
  10. Niimura M, Isoo N, Takasugi N, Tsuruoka M, Ui Tei K, Saigo K, et al. Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions. J Biol Chem. 2005;280:12967-75 pubmed
    ..precursor protein and Notch, and requires the formation of a protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 for its activity...
  11. Smith O. Biomedicine. Nota bene. In the nic of time. Science. 2001;294:2118 pubmed
  12. Wildonger J, Mann R. Evidence that nervy, the Drosophila homolog of ETO/MTG8, promotes mechanosensory organ development by enhancing Notch signaling. Dev Biol. 2005;286:507-20 pubmed
    ..We propose a model in which nvy acts downstream of ac and sc to promote the SOP fate by transiently strengthening the Dl signal emanating from the SOP. ..
  13. Koelzer S, Klein T. Regulation of expression of Vg and establishment of the dorsoventral compartment boundary in the wing imaginal disc by Suppressor of Hairless. Dev Biol. 2006;289:77-90 pubmed
    ..Thus, de-repression of its target genes obscures the involvement of Su(H) in this process. Furthermore, we provide evidence that Dx does not signal in a Su(H)-independent manner as has been suggested previously. ..
  14. Nahvi A, Shoemaker C, Green R. An expanded seed sequence definition accounts for full regulation of the hid 3' UTR by bantam miRNA. RNA. 2009;15:814-22 pubmed publisher
    ..Further support for the potential contribution of the 3-9 seed register to microRNA-mediated gene regulation is provided by the experimental validation of several novel bantam targets identified with a more relaxed search algorithm. ..
  15. Nairz K, Stocker H, Schindelholz B, Hafen E. High-resolution SNP mapping by denaturing HPLC. Proc Natl Acad Sci U S A. 2002;99:10575-80 pubmed
    ..With the example of mapping mutations to the Drosophila nicastrin locus, we discuss the benefits of this method, evaluate the frequency of closely linked and potentially ..
  16. Mahoney M, Parks A, Ruddy D, Tiong S, Esengil H, Phan A, et al. Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers. Genetics. 2006;172:2309-24 pubmed
    ..We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology...
  17. Jutras I, Laplante A, Boulais J, Brunet S, Thinakaran G, Desjardins M. Gamma-secretase is a functional component of phagosomes. J Biol Chem. 2005;280:36310-7 pubmed
    ..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 ..
  18. Michaki V, Guix F, Vennekens K, Munck S, Dingwall C, Davis J, et al. Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-? production by altering Nicastrin maturation and intracellular localization. J Biol Chem. 2012;287:1100-11 pubmed publisher
    ..knock-out cells due to the altered levels, post-translational modification, and subcellular localization of Nicastrin. Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered ?-..
  19. Singh J, Mlodzik M. Hibris, a Drosophila nephrin homolog, is required for presenilin-mediated Notch and APP-like cleavages. Dev Cell. 2012;23:82-96 pubmed publisher
    ..Thus, Hbs/Nephrin appear to share a general requirement in Psn/?-secretase regulation and associated processes. ..
  20. Lai E. Notch signaling: control of cell communication and cell fate. Development. 2004;131:965-73 pubmed
    ..This primer describes the mechanism of Notch signal transduction and how it is used to control the formation of biological patterns. ..
  21. Jia D, Tamori Y, Pyrowolakis G, Deng W. Regulation of broad by the Notch pathway affects timing of follicle cell development. Dev Biol. 2014;392:52-61 pubmed publisher
    ..Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway. ..