PUBLICATION
The Biochemical and Genetic Odyssey to the Function of a Nicastrin-Like Protein
- Authors
- Haffner, C., and Haass, C.
- ID
- ZDB-PUB-060816-32
- Date
- 2004
- Source
- Neuro-degenerative Diseases 1(4-5): 192-195 (Journal)
- Registered Authors
- Haass, Christian
- Keywords
- none
- MeSH Terms
-
- Amyloid Precursor Protein Secretases
- Animals
- Aspartic Acid Endopeptidases
- Endopeptidases/genetics
- Endopeptidases/metabolism
- Membrane Glycoproteins/genetics*
- Membrane Glycoproteins/metabolism
- Membrane Glycoproteins/physiology*
- Signal Transduction/physiology
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- PubMed
- 16908989 Full text @ Neurodegener. Dis.
Citation
Haffner, C., and Haass, C. (2004) The Biochemical and Genetic Odyssey to the Function of a Nicastrin-Like Protein. Neuro-degenerative Diseases. 1(4-5):192-195.
Abstract
gamma-Secretase is a high-molecular-weight protein complex required for the proteolytic processing of various transmembrane proteins including the Alzheimer's disease-associated amyloid precursor protein and the signaling receptor Notch. One of the gamma-secretase complex components is the type I transmembrane protein nicastrin. Here we review the odyssey to a cyclopic fish, which at the end allowed the functional analysis of nicalin, a novel member of the nicastrin protein family. This 60-kDa protein is part of a previously unknown membrane protein complex unrelated to gamma-secretase and binds to Nomo (Nodal modulator, previously known as pM5), a novel 130-kDa transmembrane protein. Both proteins are highly conserved in metazoans and show almost identical tissue distribution in humans. Functional studies in zebrafish embryos and cultured human cells revealed that nicalin and Nomo collaborate to antagonize the Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping