Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells.
Testicular Sertoli cells phagocytose apoptotic spermatogenic cells in a manner depending on the membrane phospholipid phosphatidylserine (PS) expressed at the surface of the latter cell type. Our previous studies have indicated that class B scavenger receptor type I (SR-BI) is responsible for the PS-mediated phagocytosis by Sertoli cells. We examined here whether SR-BI binds directly to PS. A cell line acquired the ability to bind to PS-exposing apoptotic cells and to incorporate PS-containing liposomes when it was forced to express SR-BI. Furthermore, the extracellular domain of rat SR-BI fused with human Fc (SRBIecd-Fc) bound to PS with a dissociation equilibrium constant of 2.4 x 10(-7) m in a cell-free solid-phase assay, whereas other phospholipids including phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine were poor binding targets. The binding activity was enhanced when CaCl(2) was included in the assay or when SRBIecd-Fc was pre-treated with N-glycanase. A portion of the extracellular domain spanning amino acid positions 33 and 191 (numbered with respect to the amino terminus) fused with Fc (SRBI33-191-Fc) showed activity and phospholipid specificity equivalent to those of SRBIecd-Fc. Finally, SRBI33-191-Fc bound to the surface of apoptotic cells with externalized PS, and the injection of SRBI33-191-Fc into the seminiferous tubules of live mice increased the number of apoptotic spermatogenic cells. These results allowed us to conclude that SR-BI is a phagocytosis-inducing PS receptor of Sertoli cells.
Kawasaki
Yuki
Y
Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
Nakagawa
Akihisa
A
Nagaosa
Kaz
K
Shiratsuchi
Akiko
A
Nakanishi
Yoshinobu
Y
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018955:CD36 Antigens / Q000737:chemistry / Q000378:metabolism*; D016466:CHO Cells; D002474:Cell-Free System; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D008024:Ligands; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D010587:Phagocytosis; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051122:Scavenger Receptors, Class B; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis
D018955:CD36 Antigens; D008024:Ligands; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase