Disease relevance of nct

• Nicastrin mutant tissue displays neuronal loss or hyperplasia; these phenotypes can be rescued by targeted expression of an intracellular form of Notch [1].

High impact information on nct

• Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion [2].
• The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin [3].
• Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex [4].
• 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 S2 phagocytes [5].
• In addition, we show that Nicastrin as well as Notch are required to maintain normal R-cell morphology, because the nuclei of mutant photoreceptor neurons cannot maintain their proper position [1].

Biological context of nct

• Nic mutants and tissue clones display characteristic Notch-like phenotypes [6].

Anatomical context of nct

• Aph-1 binds to nicastrin forming an early subcomplex independent of the conserved glycines within the endoplasmic reticulum [7].
• Nicastrin controls aspects of photoreceptor neuron specification and differentiation in the Drosophila eye [1].

Physical interactions of nct

• Aph-1 and Nct may form a subcomplex that stabilizes the Psn holoprotein at an early step in gamma-secretase assembly [4].

Regulatory relationships of nct

• Further, Nicastrin is genetically required for signaling from membrane-anchored activated Notch [6].

Other interactions of nct

• Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step [8].
• Nicastrin might recruit gamma-secretase substrates into the proteolytic complex as a prerequisite for Presenilin maturation and active complex assembly [6].

References