Studies On Endocytic Pathways Of Class A Scavenger Receptor A

Class A scavenger receptor (SR-A) is a transmembrane receptor expressed mainly in macrophages. SR-A can bind with an unusually broad range of polyanionic ligands, which includes modified lipoproteins, LPS of Gramnegative bacteria, and advanced glycation end products. Its broad specificity in binding with the ligands supports the multiple functions of SR-A in macrophage growth, adhesion to the substratum, cell-cell interactions, phagocytosis, and host defense. However, the precise endocytic pathways of SR-A-mediated ligands internalization are not fully characterized.In this study, we want to address the question of whether different functions of SR-A are carried out by different endocytosis pathways. Our data demonstrated that SR-A/ligand internalization was through two endocytosis routes: clathrin- and caveolae-dependent pathways. Dosage of the ligands seems not to influence choice of the route by SR-A. Internalizations of SR-A-lipoprotein (such as acLDL) complexes primarily go through clathrin-dependent endocytosis. In contrast, macrophage apoptosis triggered by SR-A-fucoidan internalization requires caveolae-dependent endocytosis. The caveolae-dependent process activates p38 kinase and JNK signaling, whereas the clathrin-mediated endocytosis elicits ERK signaling. Our results suggest that different SR-A endocytic pathways have distinct functional consequences due to the activation of different signaling cascades in macrophages.