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

• Published in: Journal of biomedical science 2016-02, Vol.23 (27), p.27-27, Article 27
• Main Authors: Tsay, Huey-Jen, Huang, Yung-Cheng, Chen, Yi-Jen, Lee, Yun-Hao, Hsu, Shu-Meng, Tsai, Keng-Chang, Yang, Cheng-Ning, Huang, Fong-Lee, Shie, Feng-Shiun, Lee, Lin-Chien, Shiao, Young-Ji
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino Acid Substitution; Amyloid beta-Peptides; Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cercopithecus aethiops; COS Cells; Cystine; Glycosylation; HEK293 Cells; Histopathology; Humans; Mutation, Missense; Peptides; Protein Structure, Tertiary; Protein Transport - genetics; Proteins; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Serine-Arginine Splicing Factors
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-016-0244-5

The 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. We 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. Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAβ internalization.