References
Query Results -- Details
MGI Accession ID: MGI:3835738
J Number: J:145671
Other Accession IDs:
Title: A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
Authors: Ma QH; Futagawa T; Yang WL; Jiang XD; Zeng L; Takeda Y; Xu RX; Bagnard D; Schachner M; Furley AJ; Karagogeos D; Watanabe K; Dawe GS; Xiao ZC
Journal: Nat Cell Biol
Volume: 10
Issue: 3
Date: 2008 Mar
Year: 2008
Pages: 283-94
Review Status: Peer Reviewed
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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