A TAG on to the neurogenic functions of APP |
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| Authors: | Quan-Hong Ma Dominique Bagnard Zhi-Cheng Xiao Gavin S Dawe |
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| Affiliation: | 1.Institute of Molecular and Cell Biology; Singapore;2.Department of Clinical Research; Singapore General Hospital; Singapore;3.INSERM U575; Physiopathologie du Systeme Nerveux; Centre de Neurochimie; Strasbourg, France;4.Department of Anatomy; Yong Loo Lin School of Medicine; Singapore;5.Department of Pharmacology; Yong Loo Lin School of Medicine; Singapore;6.Neurobiology and Ageing Programme; Centre for Life Sciences; National University of Singapore; Singapore |
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| Abstract: | The proteolytic processing of amyloid β precursor protein (APP) has long been studied because of its association with the pathology of Alzheimer''s disease (AD). The ectodomain of APP is shed by α- or β-secretase cleavage. The remaining membrane bound stub can then undergo regulated intramembrane proteolysis (RIP) by γ-secretase. This cleavage can release amyloid β (Aβ) from the stub left by β-secretase cleavage but also releases the APP intracellular domain (AICD) after α- or β-secretase cleavage. The physiological functions of this proteolytic processing are not well understood. We compare the proteolytic processing of APP to the ligand-dependent RIP of Notch. In this review, we discuss recent evidence suggesting that TAG1 is a functional ligand for APP. The interaction between TAG1 and APP triggers γ-secretase-dependent release of AICD. TAG1, APP and Fe65 colocalise in the neurogenic ventricular zone and in fetal neural progenitor cells in vitro. Experiments in TAG1, APP and Fe65 null mice as well as TAG1 and APP double-null mice demonstrate that TAG1 induces a γ-secretase- and Fe65-dependent suppression of neurogenesis.Key words: Amyloid β precursor protein, APP, TAG1, AICD, Fe65, neurogenesis, Alzheimer''s disease |
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