Localization of Class A Scavenger Receptors (SR‐A) in Lipid Rafts

SR‐A are multifunctional receptors that mediate macrophage adhesion and ligand endocytosis. Each of these functions are associated with specific intracellular motifs of the receptor, but the possibility that SR‐A function is regulated by localization in different membrane domains, especially lipid rafts, has not been studied. To assess this possibility, we used microscopic and cell fractionation protocols to examine SR‐A localization in cells. We show that in primary macrophages and stably transfected HEK cells, SR‐A colocalizes with markers for the endocytic pathway (e.g., clathrin), and markers of lipid rafts [e.g., caveolin and cholera toxin B (CTB)]. Using an optimized cell fractionation protocol, we found that about 20% of cellular SR‐A localized in cholesterol‐rich lipid raft fractions. To address the functional significance of SR‐A localization in lipid rafts, the localization of a truncated SR‐A receptor (SR‐A Δ1–49 ), which mediates cell adhesion but not endocytosis was examined in stably transfected HEK cells. As expected, SRA Δ1–49 did not colocalize with clathrin, but like the full‐length receptor, colocalized with CTB and was isolated in lipid raft fractions. Together, our results demonstrate that SR‐A localizes in lipid raft domains and suggest that this localization correlates with the ability of SR‐A to mediate cell adhesion. Support by R01HL089588