Doctor of Philosophy (PHD)
Molecular and Cellular Pharmacology (Medicine)
Date of Defense
First Committee Member
Charles W. Luetje - Committee Chair
Second Committee Member
Jeffrey L. Goldberg - Committee Member
Third Committee Member
John L. Bixby - Committee Member
Fourth Committee Member
Vladlen Z. Slepak - Mentor
Fifth Committee Member
Donald F. Ready - Outside Committee Member
Phototransduction is a well characterized system for study of G protein coupled receptor (GPCR) signaling. The GPCR rhodopsin couples to the heterotrimeric G protein transducin. Light-stimulated activation of transducin in turn activates phosphodiesterase (PDE), leading to closure to cGMP-gated channels and inhibition of glutamate release. Rod and cone photoreceptors are highly polarized neurons consisting of the outer segment (OS) where phototransduction biochemistry occurs, the inner segment containing mitochondria and other organelles, the nuclear layer, an axon, and a glutamatergic synapse. Upon illumination, activated G protein transducin redistributes from the rod OS (where it is localized in the dark) to the inner compartments of the cell. Interestingly, cone transducin does not translocate in light. Opposite to this, visual arrestin migrates from the inner compartments to the OS, where it binds to rhodopsin. Previous reports from other groups and our lab argue for either an active or passive mechanism for transducin and arrestin redistribution. Our lab has shown that arrestin migration occurs by diffusion which is restricted by molecular sinks (Nair et al, 2005b). The focus of my dissertation was to unravel the molecular mechanism of rod transducin translocation. Specifically, I found energy (ATP) was not required for transducin movement within photoreceptors. Also, I found that the disc membranes of the rod outer segments as well as protein-protein interactions with retinal guanylate cyclase serve to restrict transducin diffusion through the cell. In addition, I used the insights gained from these studies of transducin to re-examine the relationship of other G proteins' subcellular localization and signal transduction. Ultimately, I found that most G proteins do not undergo subunit dissociation under physiological activating conditions.
G Protein; Signal Transduction; Subcellular Localization; Photoreceptors; Neurons; Transducin
Rosenzweig, Derek Hadar, "Light-Induced Relocalization of the Photoreceptor G Protein Transducin is Mediated by Binding Partner-Restricted Diffusion: New Insights into G Protein Subunit Dissociation" (2008). Open Access Dissertations. 172.