Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor

Dev Cell. 2002 Jan;2(1):69-78. doi: 10.1016/s1534-5807(01)00105-8.


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. Nic mutants and tissue clones display characteristic Notch-like phenotypes. Genetic and inhibitor studies indicate a function for Nicastrin in the gamma-secretase step of Notch processing, similar to Presenilin. Further, Nicastrin is genetically required for signaling from membrane-anchored activated Notch. In the absence of Nicastrin, Presenilin is destabilized and mature C-terminal subunits are absent. Nicastrin might recruit gamma-secretase substrates into the proteolytic complex as a prerequisite for Presenilin maturation and active complex assembly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Animals
  • Drosophila / genetics*
  • Drosophila Proteins
  • Endopeptidases / metabolism*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mutation / physiology
  • Presenilin-1
  • Receptors, Notch
  • Signal Transduction / physiology


  • Drosophila Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • N protein, Drosophila
  • Presenilin-1
  • Receptors, Notch
  • nicastrin protein
  • Amyloid Precursor Protein Secretases
  • Endopeptidases