Di-leucine Motif Mediates Lipid Internalization In Scavenger Receptor A

Scavenger receptor A (SR-A) has an important role in involving in the pathogenesis of atherosclerosis. SR-A endocytosis of Ac-LDL depends on the clathrin-coated pit .Di-leucine signal motif is able to support the endocytosis of plasma membrane proteins. A di-leucine pair is located at the cytoplasmic domains in human, bovine, and rabbit scavenger receptors. To investigate the role of the di-leucine signal sequences in lipid metabolism in Chinese hamster ovary (CHO) cells, we constructed a SR-A mutant by substituting the di-leucine motif in human SR-A by Alanines. Receptor expression decreased and amount of cell-internalized Dil-AcLDL did greater. SR-A and clathrin overlapped essentially by immunofluorescence microscopy and immunoprecipitation. Di-leucine motif SR-A mutant linked to clathrin by immunoprecipitation, however, dual labeling of SR-A and clathrin didn't overlap essentially by immunofluorescence microscopy. Furthermore, to elucidate whether the di-leucine motif has the relation with the other motifs, deleting the 1 to 27 amino acids (SR-A_Δ1-27) which contain some motifs, such as VXFD, and the di-leucine-SR-A_Δ1-27 mutant were constructed. SR-A_Δ1-27 and SR-Aai-27 mutant increased SR-A expression. However, SR-A_Δ1-27 mutant...