PREIMPLANTATION MOUSE EMBRYOS EXPRESS A CELL-SURFACE RECEPTOR FOR TISSUE-PLASMINOGEN ACTIVATOR

The serine protease tissue-plasminogen activator (t-PA) has previously been shown to be intracellular in mouse secondary oocytes and extrace llular in fertilized eggs. Here we demonstrate that extracellular t-PA activity is bound to the surface of the fertilized egg. The level of t-PA activity associated with preimplantation mouse embryos decreases in the 2-cell stage embryo, then increases in 4-cell and morula stage embryos. However, morulae grown in culture from fertilized eggs lack t -PA activity but are able to bind exogenously added mouse t-PA. Additi onally, northern analysis indicates that preimplantation embryos do no t contain detectable levels of t-PA mRNA. Therefore, the enzyme activi ty associated with 4-cell and morula stage embryos in vivo is derived from t-PA present in the oviduct lumen that binds the embryo, and not from protein produced from translation of embryonic mRNA. The binding activity is species and protein specific in that neither mouse urokina se-type plasminogen activator (u-PA) nor human t-PA bind to cultured m orulae. Furthermore, binding activity is dose-dependent and saturable, and does not require the active site of t-PA. These data indicate tha t a cell surface-specific t-PA-binding activity exists in the preimpla ntation mouse embryo and may localize function and concentrate the pro teolytic activity of t-PA in early mouse development.