Extracellular stimuli are transmitted to intracellular effectors by signaling cascades that involve interactions of macromolecules. The present research proposal introduces undergraduate students to investigate the functional implications of two interacting proteins: G protein subunit Galpha0, a brain-enriched cell signal protein, and the Purkinje cell protein 2 (Pcp2), a protein which is only expressed in the cerebellum and the eye, and which is depleted in degenerated Purkinje cells. Cerebellar Purkinje cells are essential for integrating sensory and motor input and are known to degenerate in a variety of neurological disorders. While the function of Pcp2 remains unknown, its interaction with G protein Galpha0 suggests that the two proteins may function in a cell signal pathway important during cerebellar development. The working hypothesis for the proposed research is that interaction of Galpha0 and Pcp2 is part of a cell signaling pathway for normal cerebellum development. To test the hypothesis, cell culture, immunohistochemistry, immunocytochemistry, and behavioral studies of double knock-out mice will be performed. The two specific aims are: 1) to co-localize Galpha0 and Pcp2 at the cellular and subcellular levels; 2) to analyze the phenotypes of mice lacking both Galpha0 and Pcp2. Results from these experiments will provide information on the functional relationship between Galpha0 and Pcp2, which is likely to be important in the signaling cascade during neuronal development and disorders, and will have important implications for understanding the fundamental role of G protein in the nervous system.
| Redd, Kacy J; Oberdick, John; McCoy, John et al. (2002) Association and colocalization of G protein alpha subunits and Purkinje cell protein 2 (Pcp2) in mammalian cerebellum. J Neurosci Res 70:631-7 |
