國家衛生研究院 NHRI:Item 3990099045/9561
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    題名: Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO
    作者: Tsay, HJ;Huang, YC;Chen, YJ;Lee, YH;Hsu, SM;Tsai, KC;Yang, CN;Huang, FL;Shie, FS;Lee, LC;Shiao, YJ
    貢獻者: Center for Neuropsychiatric Research
    摘要: BACKGROUND: The accumulation of soluble oligomeric amyloid-beta peptide (oAbeta) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer's disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAbeta clearance by microglia while glycan moiety and scavenger receptor cysteine-rich (SRCR) domain may play the critical role. Macrophage receptor with collagenous structure (MARCO), another member of class A superfamily with a highly conserved SRCR domain, may also play the similar role on oAbeta internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAbeta internalization remains unclear. RESULT: We found that oAbeta internalization was diminished in the cells expressing SR-AI harboring mutations of dual N-glycosylation sites (i.e. N120Q-N143Q and N143Q-N184Q) while they were normally surface targeted. Normal oAbeta internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at beta-sheet and alpha-helix and on disulfide bone formation obstructed receptor's N-glycosylation and surface targeting. CONCLUSION: Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAbeta internalization.
    日期: 2016-02-18
    關聯: Journal of Biomedical Science. 2016 Feb 18;23:Article number 27.
    Link to: http://dx.doi.org/10.1186/s12929-016-0244-5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000370336600001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84958225249
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