Testis

Heterophilic Binding of the Adhesion Molecules Poliovirus Receptor and Immunoglobulin Superfamily 4A in the Interaction Between Mouse Spermatogenic and Sertoli Cells

Abstract
The cell adhesion molecule immunoglobulin superfamily 4A (IGSF4A) is expressed on the surface of spermatogenic cells in the mouse testis. During spermatogenesis, IGSF4A is considered to bind to another membrane molecule on the surface of Sertoli cells in a heterophilic manner. To identify this unknown partner of IGSF4A, we generated rat monoclonal antibodies against membrane proteins of mouse Sertoli cells in primary culture. From these monoclonal antibodies, we isolated a clone that immunostains Sertoli cells and at the same time reacts with the product of immunoprecipitation of the homogenate of mouse testis with anti-IGSF4A antibody. Subsequently, to identify the Sertoli cell membrane protein recognized by this monoclonal antibody, we performed expression cloning of a cDNA library from the mouse testis. As a result, we identified poliovirus receptor (PVR), another IGSF-type cell adhesion molecule, as the binding partner of IGSF4A. The antibodies against PVR and IGSF4A immunoprecipitated each other's antigen in the homogenate of mouse testis. Immunoreactivity for PVR was present in Sertoli cells but not in spermatogenic cells at all stages of spermatogenesis. Overexpression of PVR in TM4, a mouse Sertoli cell line, increased its capacity to adhere to Tera-2, a human cell line expressing IGSF4A, by more than three fold. These findings suggest that the heterophilic binding between PVR and IGSF4A is responsible, at least partly, for the interaction between Sertoli and spermatogenic cells during mouse spermatogenesis.

Key words: Testis • Sertoli cells • Spermatogenesis

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