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This article is part of the supplement: Molecular Neurodegeneration: Basic biology and disease pathways

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

Huey-Jen Tsay

  • Correspondence: Huey-Jen Tsay

Author Affiliations

Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan

Molecular Neurodegeneration 2013, 8(Suppl 1):P43  doi:10.1186/1750-1326-8-S1-P43

The electronic version of this article is the complete one and can be found online at:

Published:13 September 2013

© 2013 Tsay; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.


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.


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.