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Nat Cell Biol. 2008 Mar;10(3):283-94. doi: 10.1038/ncb1690. Epub 2008 Feb 17.

A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.

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  • 1Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.

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  • Nat Cell Biol. 2008 Apr;10(4):497.

Abstract

The release of amyloid precursor protein (APP) intracellular domain (AICD) may be triggered by extracellular cues through gamma-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 gamma-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.

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PMID:
18278038
[PubMed - indexed for MEDLINE]
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