The sodium hydrogen exchanger (NHE) is a membrane bound protein involved in regulating many important cellular functions. How a cell moves is a complex series of events synchronized by a variety of different proteins. NHE is one of the proteins critical in directing cell movement as the exchanger acts to polarize the cell and coordinates the cytoskeleton. How NHE controls cell motility is only partially understood. This project will investigate the phosphorylation of the intracellular tail of NHE by two protein kinases, Ribosomal S-6 Kinase (RSK) and RhoA Kinase (ROCK). The hypothesis of this project is that both RSK and ROCK function to regulate NHE's role in cell movement. This project will first determine where ROCK binds and phosphorylates NHE and then identify how each of these phosphorylation sites coordinates the effects of NHE including cytoskeletal organization, directed cell motility, and protein-protein interactions. NHE is one of several transport proteins thought to be involved in controlling cell polarity, cytoskeletal organization and the formation of signaling complexes in a wide variety of cell types. The results of this project will contribute our understanding of an important growing model explaining the cell biology of cytoskeletal regulation and motility.
Broader Impacts: A significant portion of this project is to provide realistic and meaningful research for undergraduates. This project is designed to fully immerse students into a research experience and allow students to benefit fully from the incorporation of research both within the curriculum and outside the curriculum at the university. The investigators have a long track record of commitment and excellence in training undergraduate researchers. Alumni from their labs have gone onto graduate school at UCSD, MIT, Yale, U of MN, Iowa U and many industrial positions. This project will involve undergraduates in important aspects of biochemistry and cellular biology research and together, this work will further the understanding of transport proteins as these membrane proteins aid in regulating cell migration events. A previously funded RUI Award provided research opportunities for 21 undergraduates and 8 high school students. Of these 29 students, 19 were women, 3 were Native Americans, and 2 were Hispanic. Funding this research project will sustain the investigator?s ability to provide well-trained undergraduates to enter graduate school, professional school, and the workforce. Specifically this project will provide another 12 to 15 undergraduates and 2 to 3 high school students research experiences outside the curriculum that will equate to 24 to 30 academic years of research experience. In addition, another 18 to 24 students will gain one year of research experience each as part of a year-long, 10 credit senior capstone course for the Biochemistry and Biotechnology Major. Finally, 9 students in the group will be provided the opportunity to participate in a full time summer research experience.
