Ellen R. Weiss, Ph.D.

Weiss
erweiss@med.unc.edu

Lab Personnel

Weiss Chrispell 2 Weiss Dong 2 Weiss Osawa 2
Weiss Xiong 2

Professor

  • B.A., Franklin and Marshall College, 1978
  • Ph.D., University of Tennessee, 1985
  • Postdoc, University of Massachusetts, 1985-88
  • Postdoc, National Jewish Center for Immunology and Respiratory Medicine, 1988-89

Funding Sources

  • National Eye Institute

Research Interests

The vertebrate retina contains two classes of light-sensing neurons, or photoreceptor cells: rods and cones. Rods are responsible for dim light vision. Cones operate in bright light and function over a broader range of light intensities than rods. There are 3 types of cones, which are responsible for our ability to distinguish colors. Rods and cones detect light via the G protein-coupled receptors (GPCRs), rhodopsin and the cone opsins, respectively. These receptors activate retina-specific G proteins that initiate signaling cascades, resulting in hyperpolarization of the rod and cone cells and signal transmission to neurons that make up the inner retina. These inner retina neurons ultimately transmit signals to the ganglion cells, which make up the optic nerve and communicate the visual signal to the brain.

Like other GPCRs, termination of rhodopsin and the cone opsin signaling is mediated in part via phosphorylation by the retina-specific G protein-coupled receptor kinases, GRK1 and GRK7. Signal termination is important in recovery of the cells from light exposure and adaptation to different light environments, allowing the retina to operate under a broad range of continually changing light intensities. Our laboratory is interested in understanding the participation of GRK1 and GRK7 in recovery and adaptation in cones.

Weiss Image

Recently, we became interested in the role of cAMP in visual signaling. We discovered that cAMP-dependent protein kinase (PKA) phosphorylates GRK1 and GRK7 in a light-dependent manner in vivo. Because cAMP levels in rods and cones are regulated by light, phosphorylation of GRK1 and GRK7 by PKA may affect their role in phototransduction and light adaptation. Our studies will focus on understanding the effect of phosphorylation on the activities and functions of GRK1 and GRK7 in vivo, the role of phosphatases in regulating the levels of the phosphorylation of these GRKs and mechanisms that control PKA activity in photoreceptor cells. Biochemical, molecular and electrophysiological approaches in mice and zebrafish will be used for these studies.

Weiss Image 2

Selected Publications

PubMed 1

  • 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.
  • Lobanova, E.S., R. Herrmann, S. Finkelstein, B. Reidel, N.P. Skiba, W.T. Deng, R. Jo, E.R. Weiss, W.W. Hauswirth, and V.Y. Arshavsky. 2010. Mechanistic basis for the failure of cone transducin to translocate: why cones are never blinded by light. J. Neurosci. 30:6815-6824.
  • 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., M.H. Ducceschi, T.J. Horner, A. Li, C.M. Craft, and S. Osawa. 2001. Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction. J. Neurosci. 21:9175-9184.
  • Weiss, E.R., D. Raman, S. Shirakawa, M.H. Ducceschi, P.T. Bertram, F. Wong, T.W. Kraft, and S. Osawa. 1998. The cloning of GRK7, a candidate cone opsin kinase, from cone- and rod-dominant mammalian retinas. Mol. Vis. 4:27.