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Heterophilic Binding of the Adhesion Molecules Poliovirus Receptor and Immunoglobulin Superfamily 4A in the Interaction Between Mouse Spermatogenic and Sertoli Cells¹

Department of Histology and Embryology,³ Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan Department of Pharmaceutics,⁴ Kyoritsu University of Pharmacy, Tokyo 105-8512, Japan Department of Surgical Pathology,⁵ Kobe University Medical School, Kobe 650-0017, Japan Division of Pharmaceutical Sciences,⁶ Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan Tumor Suppression and Functional Genomics Project,⁷ National Cancer Center Research Institute, Tokyo 104-0045, Japan Developmental Research Laboratories,⁸ Shionogi and Company, Osaka 561-0825, Japan

ABSTRACT

The cell adhesion protein immunoglobulin superfamily 4A (IGSF4A) is expressed on the surfaces of spermatogenic cells in the mouse testis. During spermatogenesis, IGSF4A is considered to bind to the surface of Sertoli cells in a heterophilic manner. To identify this unknown partner of IGSF4A, we generated rat monoclonal antibodies against the membrane proteins of mouse Sertoli cells grown in primary culture. Using these monoclonal antibodies, we isolated a clone that immunostained Sertoli cells and reacted with the product of immunoprecipitation of the homogenate of mouse testis with anti-IGSF4A antibody. Subsequently, to identify the Sertoli cell membrane protein that is 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), which is another IGSF-type cell adhesion molecule, as the binding partner of IGSF4A. The antibodies raised against PVR and IGSF4A immunoprecipitated both antigens 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 more than three-fold its capacity to adhere to Tera-2, which is a human cell line that expresses IGSF4A. These findings suggest that the heterophilic binding of PVR to IGSF4A is responsible, at least in part, for the interaction between Sertoli and spermatogenic cells during mouse spermatogenesis.

CD155,, Necl-2, Necl-5, SgIGSF, spermatogenesis, testis, TSLC1

¹Supported by grants-in-aid from the Ministry of Education, Science and Culture of Japan and the Honjin Foundation in Kanazawa University.

Correspondence: ²Tomohiko Wakayama, Department of Histology and Embryology, Graduate School of Medical Science, 13–1 Takara-machi, Kanazawa 920-8640, Japan. FAX: 81 76 234 4220; e-mail: twaka{at}basic.m.kanazawa-u.ac.jp

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