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Gene Review

Ncstn  -  nicastrin

Rattus norvegicus

Synonyms: Nicastrin
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Psychiatry related information on Ncstn


High impact information on Ncstn

  • Presenilin forms an active gamma-secretase complex together with Nicastrin (NCT), APH-1, and PEN-2, which among other substrates cleaves the beta-amyloid precursor protein (beta-APP) generating the amyloid beta-peptide and the beta-APP intracellular domain [2].
  • Here we have identified dual targeting sequences (for endoplasmic reticulum and mitochondria) in NCT and showed expression of NCT in mitochondria by immunoelectron microscopy [2].
  • In addition, active sites of synaptogenesis, the base of the external granular layer and glomeruli, contained PS1 fragments and smaller amount of NCT [3].
  • Furthermore, protease protection assays confirmed that nicastrin is contained in the outer lysosomal membrane, rather than in an internalized vesicle awaiting degradation, and that it is properly orientated with its amino-terminus facing the lysosomal lumen with its carboxyl-terminus facing the cytosol [4].
  • The immunoreactivities of both presenilin-1 and nicastrin were also observed at the sarcolemma of muscle fibers [1].

Anatomical context of Ncstn


Analytical, diagnostic and therapeutic context of Ncstn


  1. Normal distribution of presenilin-1 and nicastrin in skeletal muscle and the differential responses of these proteins after denervation. Sakuma, K., Nakao, R., Yamasa, Y., Yasuhara, M. Biochim. Biophys. Acta (2006) [Pubmed]
  2. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. Hansson, C.A., Frykman, S., Farmery, M.R., Tjernberg, L.O., Nilsberth, C., Pursglove, S.E., Ito, A., Winblad, B., Cowburn, R.F., Thyberg, J., Ankarcrona, M. J. Biol. Chem. (2004) [Pubmed]
  3. Transient abundance of presenilin 1 fragments/nicastrin complex associated with synaptogenesis during development in rat cerebellum. Uchihara, T., Sanjo, N., Nakamura, A., Han, K., Song, S.Y., St George-Hyslop, P., Fraser, P.E. Neurobiol. Aging (2006) [Pubmed]
  4. Nicastrin is a resident lysosomal membrane protein. Bagshaw, R.D., Pasternak, S.H., Mahuran, D.J., Callahan, J.W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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