Notch Cleavage: Nicastrin Helps Presenilin Make the Final Cut
نویسنده
چکیده
Presenilin is thought to be the proteolytic component of gamma-secretase, responsible for the intramembranous cleavage of substrates that include the activated Notch receptor. Recent studies have identified the novel protein Nicastrin as another essential component of the Presenilin/gamma-secretase complex.
منابع مشابه
Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype.
Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) tha...
متن کاملAph-2/Nicastrin An Essential Component of γ-Secretase and Regulator of Notch Signaling and Presenilin Localization
The Notch signaling pathway plays a role in cell fate specification in many metazoans. A critical aspect of Notch activation involves proteolysis of the Notch receptor. This cleavage event requires Presenilin as a component of a large multiprotein complex, gamma-secretase. This complex mediates a similar cleavage event of the beta-amyloid precursor protein (APP). The transmembrane protein Nicas...
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Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosyl...
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The role of Notch signaling in general and presenilin in particular was analyzed during mouse somitogenesis. We visualize cyclical production of activated Notch (NICD) and establish that somitogenesis requires less NICD than any other tissue in early mouse embryos. Indeed, formation of cervical somites proceeds in Notch1; Notch2-deficient embryos. This is in contrast to mice lacking all preseni...
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Alzheimer's disease (AD) is caused by the cerebral deposition of beta-amyloid (Abeta), a 38-43-amino acid peptide derived by proteolytic cleavage of the amyloid precursor protein (APP). Initial studies indicated that final cleavage of APP by the gamma-secretase (a complex containing presenilin and nicastrin) to produce Abeta occurred in the endosomal/lysosomal system. However, other studies sho...
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عنوان ژورنال:
- Current Biology
دوره 12 شماره
صفحات -
تاریخ انتشار 2002