Nicastrin Explained

Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the NCSTN gene.[1] [2] [3]

Function

Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein (APP) to the short Alzheimer's disease-associated peptide amyloid beta. The other proteins in the complex are PSEN1 (presenilin-1), which is the catalytically active component of the complex, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2).[4] Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell.[5] Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment.[6]

History

The protein was named after the Italian country Nicastro, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the country of Nicastro that had familial Alzheimer's disease (FAD).[7]

Interactions

Nicastrin has been shown to interact with PSEN1[8] [9] [10] [11] [12] and PSEN2.[8] [12]

Notes and References

  1. Web site: Entrez Gene: NCSTN nicastrin.
  2. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N . Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain . DNA Research . 3 . 5 . 321–9, 341–54 . Oct 1996 . 9039502 . 10.1093/dnares/3.5.321 . free .
  3. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P . Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing . Nature . 407 . 6800 . 48–54 . Sep 2000 . 10993067 . 10.1038/35024009 . 2000Natur.407...48Y . 4339220 .
  4. Kaether C, Haass C, Steiner H . Assembly, trafficking and function of gamma-secretase . Neuro-Degenerative Diseases . 3 . 4–5 . 275–83 . 2006 . 17047368 . 10.1159/000095267 . 17324271 .
  5. Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H . Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components . The Journal of Biological Chemistry . 280 . 17 . 17020–6 . Apr 2005 . 15711015 . 1201533 . 10.1074/jbc.M409467200 . free .
  6. Pardossi-Piquard R, Dunys J, Yu G, St George-Hyslop P, Alves da Costa C, Checler F . Neprilysin activity and expression are controlled by nicastrin . Journal of Neurochemistry . 97 . 4 . 1052–6 . May 2006 . 16606360 . 10.1111/j.1471-4159.2006.03822.x . 26983263 .
  7. Feldman RG, Chandler KA, Levy LL, Glaser GH . Familial Alzheimer's disease . Neurology . 13 . 10. 811–24 . Oct 1963 . 14066996 . 10.1212/wnl.13.10.811 . 32600780 .
  8. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P . Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing . Nature . 407 . 6800 . 48–54 . Sep 2000 . 10993067 . 10.1038/35024009 . 2000Natur.407...48Y . 4339220 .
  9. Haffner C, Frauli M, Topp S, Irmler M, Hofmann K, Regula JT, Bally-Cuif L, Haass C . Nicalin and its binding partner Nomo are novel Nodal signaling antagonists . The EMBO Journal . 23 . 15 . 3041–50 . Aug 2004 . 15257293 . 514924 . 10.1038/sj.emboj.7600307 .
  10. Baulac S, LaVoie MJ, Kimberly WT, Strahle J, Wolfe MS, Selkoe DJ, Xia W . Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates . Neurobiology of Disease . 14 . 2 . 194–204 . Nov 2003 . 14572442 . 10.1016/S0969-9961(03)00123-2 . 10.1.1.624.6715 . 53205510 .
  11. Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, Luthra A, Mount HT, Tandon A, Fraser PE, St George-Hyslop P . APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes . The Journal of Biological Chemistry . 278 . 9 . 7374–80 . Feb 2003 . 12471034 . 10.1074/jbc.M209499200 . free .
  12. Lee SF, Shah S, Li H, Yu C, Han W, Yu G . Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch . The Journal of Biological Chemistry . 277 . 47 . 45013–9 . Nov 2002 . 12297508 . 10.1074/jbc.M208164200 . free .

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