The CCT/TRiC Complex Is Involved in Mediating Sperm-Oocyte Interaction.

Abstract

Sperm-oocyte interactions are among the most remarkable processes in cell biology. These cellular recognition events are initiated by an exquisitely specific adhesion of free-swimming spermatozoa to the zona pellucida, an acellular matrix that surrounds the ovulated oocyte. Decades of research focusing on this interaction have led to the establishment of a widely held paradigm that the zona pellucida receptor is a single molecular entity that is constitutively expressed on the sperm cell surface. In stark contrast, we have employed the novel techniques of blue native polyacrylamide gel electrophoresis, far-Western blotting and proximity ligation to secure the first direct evidence in support of a novel hypothesis that suggests that zona pellucida binding is mediated by multimeric sperm receptor complex(es). Furthermore, we show that one such complex is assembled on the sperm surface through the concerted action of a family of molecular chaperones, comprising the chaperonin containing TCP1 complex (CCT/TRiC), during capacitation, the final phase of sperm maturation. Among the potential CCT/TRiC complex interacting proteins that could account for its zona affinity, we have identified zona pellucida binding protein 1, zona pellucida binding protein 2, and zona pellucida 3 receptor as compelling candidates. Collectively, these data provide an important biochemical insight into the molecular basis of sperm-zona pellucida interaction and a plausible explanation for how sperm gain their ability to fertilize. (poster)