Roles of focal adhesion, phosphoinositide lipids and cytoskeleton in Caenorhabditis elegans ovulation.

Includes bibliographical references (p. 92-102)Ovulation provides us with a robust in vivo model to study how the gonad contracts and releases eggs. By dissecting different molecules and signaling pathways in the process of gonad contraction, I have gained insights on how focal adhesion, phosphoinositide lipids, and cytoskeleton coordinate ovulation, a rhythmic behavior of C. elegans. Integrin plays an essential role in ovulation via the phosphoinositide signaling pathway. My studies have determined that ovulation defects caused by RNAi of pat-3/ [beta] integrin or ECM molecules is suppressed by increased IP3 signaling, demonstrating that cell-ECM interaction is essential for ovulation, which is mediated via IP3 signaling. Additional studies have demonstrated that loss of other focal adhesion molecules, pat-4/ILK and unc-112/Mig-2 causes defects in gonad sheath contraction and spermatheca dilation and disrupts gonad cytoskeleton. I have also identified one more IP3 signaling gene involved in C. elegans ovulation, which is phosphatidylinositol-4-phosphate 5' kinase (ppk-1/PIP5K). ppk-1 is mainly expressed in the somatic gonad. Depletion of PPK-1 results in sterility and impairs gonad sheath contractility. Further analysis reveals that ppk-1 RNAi induced sterility can be suppressed by increased IP3 signaling and that ppk-1 is also linked to unc-54/myosin B, demonstrating that ppk-1 plays an important role in IP3 signaling and organizes cytoskeleton in somatic gonad. Taken together, these studies enable me to conclude that ovulation is a rhythmic cellular behavior that requires coordination of signaling paths: focal adhesion, phosphoinositide lipids and cytoskeleton proteins to induce timely release of a matured egg from the ovary to the spermatheca for fertilization.by Xiaojian Xu.Ph.D