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.
Date:
2016-02-18
Relation:
Journal of Biomedical Science. 2016 Feb 18;23:Article number 27.
