This project is awarded under the Minority Postdoctoral Research Fellowships and Supporting Activities Program for 2006.
The protein phosphatase calcineurin is a key mediator of the calcium (Ca2+) signal in eukaryotic cells. In Saccharomyces cerevisiae, Ca2+/calcineurin mediates the cellular response to environmental stresses, such as high temperature, high salinity and high pH. Under these conditions there is an increase in Ca2+ levels inside the cell, which activates calcineurin. Calcineurin then dephosphorylates a subset of cellular proteins, which promote cell survival. Due to the fact that calcineurin responds to a variety of environmental conditions that yeast encounter, its activity is tightly regulated to insure efficient and proper activation of the proteins that it dephosphorylates. Therefore, calcineurin's own activity is modulated not only through changes in Ca2+ levels but also through specific interactions with other proteins (binding partners). These binding partners act to regulate calcineurin's activity by several mechanisms such as compartmentalization, substrate specificity, and inhibition or activation under specific physiological conditions. Dr Martha Cyert's laboratory at Stanford University, which serves as the host laboratory for this Fellow, has identified five novel calcineurin interacting partners, Bna4p, Cin8p, Sli15p, Whi3p, and Yck1p, which are excellent candidates to function as regulators of calcineurin activity. The aim of this project is to determine the functional significance of the binding between calcineurin and these five interacting partners using a variety of approaches including genetic and biochemical techniques. In addition to providing insights into the biology of yeast cells, this research is likely to provide insights into regulatory mechanisms that function in human cells. Calcineurin has been highly conserved through evolution, and yeast calcineurin is very similar in its overall structure and identity to calcineurin found in human cells. In humans, calcineurin mediates critical Ca2+ activated regulatory processes that take place in the immune system, brain and heart. The overall goal of this study is to identify novel binding partners of calcineurin and determine the biological significance of these interactions. One aim is to uncover the specific role that these calcineurin interacting partners play in properly coordinating the activity of calcineurin. The studies proposed will add to the knowledge base of calcineurin binding proteins and thus aid in understanding the full spectrum of calcineurin activity. The studies described in this proposal will serve as a foundation for conducting Dr. Wout's independent research in the future. She plans to encourage the participation of underrepresented minority students in her research and serve as a role model for these students.
