Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO

Journal of Biomedical Science

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