- 作者: Huey-Jen Tsay, Yung-Cheng Huang, Yi-Jen Chen, Yun-Hao Lee, Shu-Meng Hsu, Keng-Chang Tsai, Cheng-Ning Yang, Fong-Lee Huang, Feng-Shiun Shie, Lin-Chien Lee and Young-Ji Shiao
- 作者服務機構: Institute of Neuroscience, Brain Research Center, National Yang-Ming University
- 中文摘要: --
- 英文摘要:
Background
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.
Result
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.
Conclusion
Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAβ internalization. - 中文關鍵字: --
- 英文關鍵字: Scavenger receptor A, MARCO, SRCR domain, N-glycosylation, Alzheimer’s disease, oligomeric β-amyloid