Nicastrin: gatekeeper of the gamma-secretase complex

Cell. 2005 Aug 12;122(3):318-20. doi: 10.1016/j.cell.2005.07.021.


The gamma-secretase intramembrane protease cleaves many type I membrane proteins including amyloid precursor protein and Notch, generating peptide fragments that are important signaling components. In this issue of Cell, Shah et al. (2005) reveal the function of nicastrin, the largest member of the gamma-secretase complex. They show that the nicastrin extracellular domain is essential for recognition of substrate by the gamma-secretase.

Publication types

  • Comment
  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Animals
  • Aspartic Acid Endopeptidases / metabolism*
  • Endopeptidases
  • Humans
  • Membrane Glycoproteins / physiology*
  • Protein Structure, Tertiary / physiology
  • Signal Transduction / physiology


  • Membrane Glycoproteins
  • nicastrin protein
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human