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Differential Regulation of Class A Scavenger Receptor (SR‐A) Function by Compartmentalization
Author(s) -
Vadali Shanthi,
Post Steven
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.652.13
Subject(s) - internalization , microbiology and biotechnology , scavenger receptor , lipid raft , cell adhesion , cytoplasm , chemistry , receptor , biology , cell , signal transduction , biochemistry , cholesterol , lipoprotein
SR‐A is a macrophage receptor with roles in the development of atherosclerosis and tissue repair following myocardial infarction. SR‐A mediates ligand internalization and macrophage adhesion; however, the mechanisms that differentially regulate these functions are not well defined. In this study, we examined whether SR‐A function is regulated by localization in cholesterol‐rich lipid rafts (LR). A detergent‐free cell fractionation protocol was used to show that SR‐A was 3‐fold enriched in LR relative to non‐raft membranes isolated from primary macrophages, THP‐1 macrophages, and stably transfected HEK cells. An association between SR‐A‐mediated cell adhesion and LR was indicated by truncating the cytoplasmic tail of SR‐A (SR‐A Δ1–49 ), which abolished receptor internalization but did not affect SR‐A‐mediated adhesion or localization in LR. Further, disrupting LR function by depleting membrane cholesterol with methyl‐beta‐cyclodextrin (MβCD) inhibited cell adhesion mediated by SR‐A, but not that mediated by SR‐A Δ1–49 . This suggests the presence of a LR‐dependent regulatory element in the cytoplasmic domain of SR‐A. In contrast to its effect on cell adhesion, MβCD treatment did not significantly affect the SR‐A‐mediated uptake of modified lipoprotein. Thus, localization of SR‐A in LR, perhaps with specific signaling proteins, is a mechanism that differentially regulates SR‐A function. Support: NIH‐HLRO1–076682 and AHA‐11PRE‐7950020.