Shoji Osawa, Ph.D.

Osawa
shoosawa@med.unc.edu

Associate Professor

  • Ph.D., Tokyo Metropolitan University, 1979

Funding Sources

  • National Eye Institute

Research Interests

My overall research interest is to study the regulatory mechanisms of signal transduction by G protein-coupled receptors using the visual system as a model. Two types of photoreceptor cells, rods and cones, mediate the response to light in the mammalian retina. Rods are responsible for vision in dim light. Cones are specialized to detect red, blue or green light through the presence of distinct light-absorbing opsins. Electrophysiological studies have determined that the response to light is more rapid in cones and that they terminate more quickly than rods. The reasons for these differences are not well understood. Most of our knowledge of phototransduction in mammals is derived from studies of the rod cells, because most mammalian retinas are 90 to 95% rods.

Osawa Image

My research addresses the reasons for differences in signal termination observed for rods and cones by examining the biochemical properties of the proteins involved in phototransduction in both cell types. One signal termination mechanism is known as receptor desensitization. In rods, signaling is turned off through the phosphorylation of rhodopsin by a G protein-coupled receptor kinase, rhodopsin kinase (GRK1), followed by the binding of arrestin. The arrestin-bound rhodopsin is no longer able to activate its G protein, transducin. We recently have cloned a novel G protein coupled receptor kinase, GRK7, from several mammalian retinas. This kinase appears to be the cone counterpart of GRK1 from immunolocalization studies in mammalian retinas, as well as in vitro biochemical analysis. We are currently analyzing the biochemical properties of this kinase in more detail and comparing its properties to GRK1.

Selected Publications

  • Osawa, S., and E.R. Weiss. 2012. A tale of two kinases in rods and cones. Adv. Exp. Med. Biol. 723:821-827.
  • Osawa, S., R. Jo, Y. Xiong, B. Reidel, N. Tserentsoodol, V.Y. Arshavsky, P.M. Iuvone, and E.R. Weiss. 2011. Phosphorylation of G Protein-coupled Receptor Kinase 1 (GRK1) Is regulated by light but independent of phototransduction in rod photoreceptors. J. Biol. Chem. 286:20923-20929.
  • Osawa, S., R. Jo, and E.R. Weiss. 2008. Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light. J. Neurochem. 107:1314-1324.
  • Liu, P., S. Osawa, and E.R. Weiss. 2005. M opsin phosphorylation in intact mammalian retinas. J. Neurochem. 93:135-144.
  • Horner, T.J., S. Osawa, M.D. Schaller, and E.R. Weiss. 2005. Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. J. Biol. Chem. 280:28241-28250.
  • Liu, P., E.D. Roush, J.A. Bruno, S. Osawa, and E.R. Weiss. 2004. Direct binding of visual arrestin to a rhodopsin carboxyl-terminal synthetic phosphopeptide. Mol. Vis. 10:712-9.
  • Raman, D., S. Osawa, V.V. Gurevich, and E.R. Weiss. 2003. The interaction with the cytoplasmic loops of rhodopsin plays a crucial role in arrestin activation and binding. J. Neurochem. 84:1040-1050.
  • Cideciyan, A.V., S.G. Jacobson, N. Gupta, S. Osawa, K.G. Locke, E.R. Weiss, A.F. Wright, D.G. Birch, and A.H. Milam. 2003. G-protein-coupled receptor kinase 1 (GRK1) and GRK7 expression and cone deactivation kinetics in enhanced S-cone syndrome (ESCS) caused by mutations in NR2E3. Invest. Ophthalmol. Vis. Sci. 44:1268-1274.
  • Zhu, X., A. Li, B. Brown, E.R. Weiss, S. Osawa, and C.M. Craft. 2002. Mouse cone arrestin expression pattern: Light induced translocation in cone photoreceptors. Mol. Vis. 8:462-471.
  • Weiss, E. R., Ducceschi, M. H., Horner, T. J., Aimin Li, Cheryl M. Craft and Osawa, S. (2001) Species-specific differences in expression of GRK7 and GRK1 in mammalian cone photoreceptor cells: implication for cone cell phototransduction. J. Neurosci. 21:9175-9184.
  • Osawa, S., Raman, D. and Weiss, E.R. (2000) Heterologous expression and reconstitution of rhodopsin with rhodopsin kinase and arrestin. Methods Enzymol. 315, 411-422.
  • Raman, D., Osawa, S. and Weiss, E.R. (1999) Binding of Arrestin to Cytoplasmic Loop Mutants of Bovine Rhodopsin. Biochemistry 38, 5117-5123.
  • Weiss, E.R., Raman, D., Shirakawa, S., Duccesschi, M.H., Bertram, P.T., Wong, F., Kraft, T.W. and Osawa,S. (1998) The cloning of GRK7, a candidate cone opsin kinase, from cone- and and rod-dominant mammalian retinas. Mol. Vis. 4, 27 (http://www.molvis.org/molvis/v4/p27).
  • Osawa, S., and E.R. Weiss. 2012. A tale of two kinases in rods and cones. Adv. Exp. Med. Biol. 723:821-827.
  • Osawa, S., R. Jo, Y. Xiong, B. Reidel, N. Tserentsoodol, V.Y. Arshavsky, P.M. Iuvone, and E.R. Weiss. 2011. Phosphorylation of G Protein-coupled Receptor Kinase 1 (GRK1) Is regulated by light but independent of phototransduction in rod photoreceptors. J. Biol. Chem. 286:20923-20929.
  • Osawa, S., R. Jo, and E.R. Weiss. 2008. Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light. J. Neurochem. 107:1314-1324.
  • Liu, P., S. Osawa, and E.R. Weiss. 2005. M opsin phosphorylation in intact mammalian retinas. J. Neurochem. 93:135-144.
  • Horner, T.J., S. Osawa, M.D. Schaller, and E.R. Weiss. 2005. Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. J. Biol. Chem. 280:28241-28250.
  • Liu, P., E.D. Roush, J.A. Bruno, S. Osawa, and E.R. Weiss. 2004. Direct binding of visual arrestin to a rhodopsin carboxyl-terminal synthetic phosphopeptide. Mol. Vis. 10:712-9.
  • Raman, D., S. Osawa, V.V. Gurevich, and E.R. Weiss. 2003. The interaction with the cytoplasmic loops of rhodopsin plays a crucial role in arrestin activation and binding. J. Neurochem. 84:1040-1050.
  • Cideciyan, A.V., S.G. Jacobson, N. Gupta, S. Osawa, K.G. Locke, E.R. Weiss, A.F. Wright, D.G. Birch, and A.H. Milam. 2003. G-protein-coupled receptor kinase 1 (GRK1) and GRK7 expression and cone deactivation kinetics in enhanced S-cone syndrome (ESCS) caused by mutations in NR2E3. Invest. Ophthalmol. Vis. Sci. 44:1268-1274.
  • Zhu, X., A. Li, B. Brown, E.R. Weiss, S. Osawa, and C.M. Craft. 2002. Mouse cone arrestin expression pattern: Light induced translocation in cone photoreceptors. Mol. Vis. 8:462-471.
  • Osawa, S., and E.R. Weiss. 2012. A tale of two kinases in rods and cones. Adv. Exp. Med. Biol. 723:821-827.
  • Osawa, S., R. Jo, Y. Xiong, B. Reidel, N. Tserentsoodol, V.Y. Arshavsky, P.M. Iuvone, and E.R. Weiss. 2011. Phosphorylation of G Protein-coupled Receptor Kinase 1 (GRK1) Is regulated by light but independent of phototransduction in rod photoreceptors. J. Biol. Chem. 286:20923-20929.
  • Osawa, S., R. Jo, and E.R. Weiss. 2008. Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light. J. Neurochem. 107:1314-1324.
  • Liu, P., S. Osawa, and E.R. Weiss. 2005. M opsin phosphorylation in intact mammalian retinas. J. Neurochem. 93:135-144.
  • Horner, T.J., S. Osawa, M.D. Schaller, and E.R. Weiss. 2005. Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. J. Biol. Chem. 280:28241-28250.
  • Liu, P., E.D. Roush, J.A. Bruno, S. Osawa, and E.R. Weiss. 2004. Direct binding of visual arrestin to a rhodopsin carboxyl-terminal synthetic phosphopeptide. Mol. Vis. 10:712-9.
  • Raman, D., S. Osawa, V.V. Gurevich, and E.R. Weiss. 2003. The interaction with the cytoplasmic loops of rhodopsin plays a crucial role in arrestin activation and binding. J. Neurochem. 84:1040-1050.
  • Cideciyan, A.V., S.G. Jacobson, N. Gupta, S. Osawa, K.G. Locke, E.R. Weiss, A.F. Wright, D.G. Birch, and A.H. Milam. 2003. G-protein-coupled receptor kinase 1 (GRK1) and GRK7 expression and cone deactivation kinetics in enhanced S-cone syndrome (ESCS) caused by mutations in NR2E3. Invest. Ophthalmol. Vis. Sci. 44:1268-1274.