The central theme of this competing P01 application is signal transduction mechanisms in reproduction, their organization and compartmentalization. The three research projects (Project 14: Akap82 and Compartmentalization of Signaling in Sperm; Project 10: Regulation of Ovarian and Placental Steroidogenesis; Project 15:Compartmentalization of Acrogranin Signaling in Embryos) focus on critical events in the achievement of pregnancy including spermatogenesis, sperm motility and capitation, the endocrine support of the reproductive tract by ovarian and placental steroid hormones, early embryo development and implantation. One core will support the Program. It is now evident that signaling cascades are highly compartmentalized, especially in germ cells, and that critical events in reproduction (e.g., ovulation; fertilization; and implantation) depend upon localized communication between cellular compartments (i.e., autocrine and paracrine communication). Moreover, signal transduction initiated by cell-cell interaction or nontraditional ligands is now known to be important in the process of capacitation, fertilization and implantation. Thus, a shift in the paradigm for studying signal transduction from classical biochemical and pharmacological approaches to strategies that merge molecular and cell biology and allow the structural organization of components of signaling systems, including scaffolding mechanisms that anchor components to specific locations, needs to be elucidated and the activities of these signal transduction pathways monitored in space and time. A major theme emphasized in the current application is the organization and compartmentalization of signaling mechanisms. An understanding of the special and temporal features of signal transduction will be critical by the design of innovative pharmacological interventions to support or suppress fertility. This demands expertise encompassing diverse research disciplines that can best be collected through a mechanism like the P01, where each of the participating investigators brings unique knowledge and technical skills. This P01 is structured to foster multiple levels of interaction including overlap in concept as well as technology.
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