A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
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A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. / Ma, Quanhong; Futagawa, Toshitaka; Yang, Wu-Lin; Jiang, Xiao-Dan; Zeng, Li; Takeda, Yasuo; Xu, Ru-Xiang; Bagnard, Dominique; Schachner, Melitta; Furley, Andrew J; Karagogeos, Domna; Watanabe, Kazutada; Dawe, Gavin S; Xiao, Zhi-Cheng.
in: NAT CELL BIOL, Jahrgang 10, Nr. 3, 3, 2008, S. 283-294.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
AU - Ma, Quanhong
AU - Futagawa, Toshitaka
AU - Yang, Wu-Lin
AU - Jiang, Xiao-Dan
AU - Zeng, Li
AU - Takeda, Yasuo
AU - Xu, Ru-Xiang
AU - Bagnard, Dominique
AU - Schachner, Melitta
AU - Furley, Andrew J
AU - Karagogeos, Domna
AU - Watanabe, Kazutada
AU - Dawe, Gavin S
AU - Xiao, Zhi-Cheng
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 10
SP - 283
EP - 294
JO - NAT CELL BIOL
JF - NAT CELL BIOL
SN - 1465-7392
IS - 3
M1 - 3
ER -