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Dev Cell. 2002 Jan;2(1):69-78.

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

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1
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract

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.

PMID:
11782315
[Indexed for MEDLINE]
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