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  • Poster presentation
  • Open Access

Cysteine-rich domain of scavenger receptor Al modulates the efficacy of surface targeting and mediates internalization of oligomeric beta amyloid

  • 1
Molecular Neurodegeneration20138 (Suppl 1) :P43

https://doi.org/10.1186/1750-1326-8-S1-P43

  • Published:

Keywords

  • Surface Target
  • Scavenger Receptor
  • Beta Amyloid
  • Matrix Adhesion
  • Collagenous Domain

Background

Scavenger receptor class A (SR-A) of microglia and macrophage mediates the internalization of oligomeric amyloid-β peptide (oAβ) and low-density lipoprotein in Alzheimer’s disease and atherosclerosis. SR-A is a member of the cysteine-rich domain (SRCR) superfamily, but the function of the SRCR domain is unclear.

Materials and methods

We investigated whether the SR-AI SRCR domain encoded by exons 10 and 11 modulates receptor surface targeting, ligand internalization, and extracellular matrix adhesion by expressing mutated SR-A variants in COS-7 cells.

Results

We found that SR-A variants with truncated exon 11 were intracellularly retained, whereas SR-A variants with further truncation into exon 10 were surface-targeted. Surface-targeted variants were fully glycosylated, whereas intracellularly-retained variants remained in high-mannose states. The fusion of exon 11 with a surface-targeted SR-A variant resulted in intracellular retention and a high-mannose state. Both the SRCR and collagenous domains mediated the ligand binding, but the collagenous domain was more important for matrix adhesion. Point mutations in a long stretch of β sheet 1, 2 and a loop region between β sheet 4 and 5 of the SRCR domain resulted in intracellular retention and a high-mannose state.

Conclusions

By identifying the function and critical motifs of the SRCR domain, our study suggests possible approaches to modulate innate immunity in Alzheimer’s disease and atherosclerosis.

Authors’ Affiliations

(1)
Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan

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