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

被引：162

作者：

Hu, Y ^{[1
]}

Ye, YH ^{[1
]}

Fortini, ME ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA

来源：

DEVELOPMENTAL CELL | 2002年 / 2卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1534-5807(01)00105-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：69 / 78

页数：10

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