Journal of Biomedical Science | |
Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO | |
Research | |
Feng-Shiun Shie1  Yung-Cheng Huang2  Lin-Chien Lee3  Young-Ji Shiao4  Keng-Chang Tsai5  Fong-Lee Huang6  Cheng-Ning Yang6  Shu-Meng Hsu7  Yun-Hao Lee7  Yi-Jen Chen7  Huey-Jen Tsay7  | |
[1] Center for Neuropsychiatric Research, National Health Research Institutes, No. 35 Keyan Road, Zhunan Town, 350, Miaoli County, Taiwan, R.O.C;Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, 112, Taipei, Taiwan, R.O.C;Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, 11220, Taipei, Taiwan, R.O.C;Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, 11221, Taipei, Taiwan, R.O.C;Institute of Biopharmaceutical Science, National Yang-Ming University, 11221, Taipei, Taiwan, R.O.C;Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, 11221, Taipei, Taiwan, R.O.C;Institute of Anatomy and Cell Biology, National Yang-Ming University, 11221, Taipei, Taiwan, R.O.C;Institute of Neuroscience, Brain Research Center, National Yang-Ming University, 11221, Taipei, Taiwan, R.O.C; | |
关键词: Scavenger receptor A; MARCO; SRCR domain; N-glycosylation; Alzheimer’s disease; oligomeric β-amyloid; | |
DOI : 10.1186/s12929-016-0244-5 | |
received in 2015-11-24, accepted in 2016-02-03, 发布年份 2016 | |
来源: Springer | |
【 摘 要 】
BackgroundThe accumulation of soluble oligomeric amyloid-β peptide (oAβ) 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 oAβ 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 oAβ internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAβ internalization remains unclear.ResultWe found that oAβ 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 oAβ internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at β-sheet and α-helix and on disulfide bone formation obstructed receptor’s N-glycosylation and surface targeting.ConclusionOur study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAβ internalization.
【 授权许可】
CC BY
© Tsay et al. 2016
【 预 览 】
Files | Size | Format | View |
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RO202311109659243ZK.pdf | 2541KB | download |
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