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- Title
A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
- Authors
Quan-Hong Ma; Futagawa, Toshitaka; Wu-Lin Yang; Xiao-Dan Jiang; Li Zeng; Takeda, Yasuo; Ru-Xiang Xu; Bagnard, Dominique; Schachner, Melitta; Furley, Andrew J.; Karagogeos, Domna; Watanabe, Kazutada; Dawe, Gavin S.; Zhi-Cheng Xiao
- Abstract
The release of amyloid precursor protein (APP) intracellular domain (AICD) may be triggered by extracellular cues through γ-secretase-dependent cleavage. AICD binds to Fe65, which may have a role in AICD-dependent signalling; however, the functional ligand has not been characterized. In this study, we have identified TAG1 as a functional ligand of APP. We found that, through an extracellular interaction with APP, TAG1 increased AICD release and triggered Fe65-dependent activity in a γ-secretase-dependent manner. TAG1, APP and Fe65 colocalized in the neural stem cell niche of the fetal ventricular zone. Neural precursor cells from TAG1−/−, APP−/− and TAG1−/−;APP−/− mice had aberrantly enhanced neurogenesis, which was significantly reversed in TAG1−/− mice by TAG1 or AICD but not by AICD mutated at the Fe65 binding site. Notably, TAG1 reduced normal neurogenesis in Fe65+/+ mice. Abnormally enhanced neurogenesis also occurred in Fe65−/− mice but could not be reversed by TAG1. These results describe a TAG1–APP signalling pathway that negatively modulates neurogenesis through Fe65.
- Subjects
AMYLOID beta-protein precursor; EXTRACELLULAR matrix; DEVELOPMENTAL neurobiology; LIGANDS (Biochemistry); MICE
- Publication
Nature Cell Biology, 2008, Vol 10, Issue 3, p283
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1690