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J. Biol. Chem., Vol. 277, Issue 30, 27559-27566, July 26, 2002
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From the 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 × 10
Phosphatidylserine Binding of Class B Scavenger Receptor Type I,
a Phagocytosis Receptor of Testicular Sertoli Cells*
,, Graduate School of Natural Science and
Technology and § Graduate School of Medical Science,
Kanazawa University, 13-1 Takara-machi, Kanazawa,
Ishikawa 920-0934, Japan
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 CaCl2 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.
*
This study was supported by a grant-in-aid for Scientific
Research from Japan Society for the Promotion of Science and grants from the Mitsubishi Foundation, Sumitomo Foundation, Hayashi Memorial Foundation for Female Natural Scientists, Honjin Foundation, and Nissan
Science Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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