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Current Alzheimer Research
ISSN (Print): 1567-2050
ISSN (Online): 1875-5828
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DOI: 10.2174/1567205011888140411163936      Price:  $95









RCAN1 Increases Aβ Generation by Promoting N-glycosylation via Oligosaccharyltransferase

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Author(s): Tan Wang, Heng Liu, Yun Wang, Changqing Liu and Xiulian Sun
Pages 1-8 (8)
Abstract:
Glycosylation is one of the major post-translational modifications, required for proper folding and functions of glycoproteins. N-glycosylation in ER is mediated by oligosaccharyltransferase (OST), an enzyme complex transferring preassembled oligosaccharide to asparagine residues of nascent polypeptide chain. Our study here indicates that regulator of calcineurin 1 (RCAN1) can enhance N-glycosylation in ER, therefore elevates the activities of β- and γ-secretase and markedly increases Aβ production. We found that RCAN1 stabilizes OST by interacting with OST component ribophorinI (RPN I). RCAN1 enhanced glycosylation of membrane proteins and glycosylation sequon GNSTVT, but has no effect on transferrin whose glycosylation was only affected by OST catalytic subunit STT3A, suggesting the effect of RCAN1 is associated with RPN I in facilitating substrate delivery. Our previous studies have shown that RCAN1 was increased in AD brains and RCAN1 overexpression induced neuronal apoptosis. Here our study showed that RCAN1 further contributes to AD pathogenesis by increasing N-glycosylation and Aβ production.
Keywords:
Aβ, alzheimer’s disease, β-secretase, γ-secretase, N-glycosylation, oligosaccharyltransferase, RCAN1
Affiliation:
Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, P. R. China