RCAN1 Increases Aβ Generation by Promoting N-glycosylation via Oligosaccharyltransferase
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.
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