A Cell Cycle Regulating Receptor Is Localized on Cell Surface and in Nuclei of Mitotically and Meiotically Dividing Cells

Abstract

We previously showed that a heterodimeric surface receptor of molecular weight 65,000 (p65) and 95,000 (p95) is expressed on the surface of proliferating cells such as activated T lymphocytes and neural precursors. This p65/p95 receptor is recognized by a monoclonal antibody and by type 3 reovirus hemagglutinin. Binding of the surface p65/p95 receptor leads to a growth arrest of mitotic cells and a consequent inhibition of proliferation. The p65/p95 receptor was demonstrated to be associated with kinase activity. Because p65/p95 is involved in the regulation of mitotic cell division, we sought to study the cellular distribution of the receptor and its possible role in meiotic cell division. Immunohistochemical labeling and flow cytometry studies were done using adult rat testes and cell lines. All cells undergoing mitotic or meiotic division in the rat testis expressed the p65/p95 receptor; cells that do not divide did not express receptors. Dividing cells had two receptor pools. As previously reported for several mitotically active tissues, a pool of receptors was localized on the cell surface. Interestingly, a pool of receptors was also seen intracellularly over the nucleus of labeled cells. The nuclear label seemed to be associated with chromosomes during specific stages of the mitotic and the two meiotic divisions, suggesting a role in the regulation of nuclear events. Further studies on this receptor and the function of the nuclear pool should provide a better understanding of the control of cell division.