The Smith Lab


photo Dr Smith Research to Prevent Blindness Foundation

Principal Investigator

W. Clay Smith, PhD
Associate Professor and Director of Research


Contact Information

(352) 273-8794




About the PI

Clay Smith 2014Dr. Smith received his BS and MS in entomology from the University of Florida in 1986, intrigued by visual function of insects. He continued this interest in graduate school at Yale University, studying retinoid metabolism in the visual process with Prof. Timothy Goldsmith, and earning his PhD in neurobiology in 1990. After a post-doctoral fellowship with Prof. Doug Kankel at Yale University studying Drosophila genetics, he moved to the Whitney Laboratory for Marine Bioscience for a post-doctoral fellowship with Dr. Barbara Battelle where he studied the molecular biology of the horseshoe crab eye. He joined UF’s Department of Ophthalmology in 1993, working with Dr. Paul Hargrave on the biochemistry of photortransduction, and then developing his own program on the molecular and cellular biology of photoreceptors. He serves as the Director of the Ocular Gene Therapy Core for production of AAV to treat blinding diseases, the Director of Research for the Department of Ophthalmology, and as co-Director with Dr. Mark Sherwood for the Center for Vision Research.

Areas of Interest

The principal focus of the Smith laboratory is on the molecular biochemistry and cell biology of the eye, with particular emphasis on the retina. The Smith Lab research has centered on canonical and non-canonical signaling pathways in photoreceptors, particularly focusing on the ancillary cascades signaled by the phototransduction elements. These signaling pathways are relevant to many degenerative and immunological diseases of the eye.

Research Summary

Photo of techs working in the labStructure/function relationships in the arrestin protein. The function of arrestin to inactivate rhodopsin in phototransduction was well established by several laboratories in the 1980’s. However, the mechanism by which arrestin selectively binds and quenches only light-activated, phosphorylated rhodopsin was unclear and has significant implications for the majority of the G-protein-coupled receptor family. Work in our lab and with a team of collaborators mapped the surface of arrestin that interacted with rhodopsin. This work was the first to demonstrate that multiple smaller conformational changes in arrestin, rather than large domain movements, were responsible for driving the selectivity of arrestin for phosphorylated, photoactivated rhodopsin, a finding that has been born out for the broader class of G-protein-coupled receptors.

  1. Sommer ME, Farrens DL, McDowell JH, Weber LA, Smith WC (2007) Dynamics of arrestin-rhodopsin interactions: loop movement is involved in arrestin activation and receptor binding. J. Biol. Chem. 282: 25560-25568.
  2. Smith WC, Dinculescu A, Peterson JJ, McDowell JH (2004) The surface of visual arrestin that binds to rhodopsin. Molec. Vision 10: 392-398.
  3. Dinculescu A, McDowell JH, Amici SA, Dugger DR, Richards N, Hargrave PA, Smith WC (2002) An insertional mutagenesis and immunochemical analysis of visual arrestin interaction with rhodopsin. J. Biol. Chem. 277: 11703-11708.
  4. Smith WC, McDowell JH, Dugger DR, Miller R, Arendt A, Popp MP, Hargrave PA (1999) Identification of regions of arrestin that bind to rhodopsin. Biochem. 38: 2752-2761.

Photo of lab frogsMechanism and function of arrestin translocation. Large-scale movements of arrestin and transducin proteins between the inner and outer segments of photoreceptor have been known for more than three decades. However, the mechanism and function of this light-driven translocation of arrestin remained a gap in our understanding of photoreceptor biology. We adapted combinations of transgenic animals expressing modified arrestin proteins and refined organotypic culture methods to demonstrate that arrestin translocation can be described in a three-phase process: 1) initiation of translocation occurs through a gated signaling process mediated by phospholipase C activation of protein kinase C to phosphorylate Bardet-Biedl Syndrome 5 protein 2) followed by passive diffusion of arrestin that accounts for much of the translocation dynamics, 3) but is facilitated by cytoskeletal microtubule components for a more rapid delivery to outer segment extremes. This work was done in my lab and with collaborators in Germany.

  1. Orisme W, Goldmann T, Li J, Bolch S, Wolfrum U, Smith WC (2010) Arrestin translocation in rod photoreceptors is signaled through phospholipase C and is an ATP-dependent process. Cellular Signaling 22:447-456. PMC2794968
  2. Reidel B, Orisme W, Goldmann T, Smith WC, Wolfrum W (2006) Molecular movements of arrestin and transducin studied in photoreceptors of organotypic cultures of mature vertebrate retinas. Vision Res. 46: 4464-4471.
  3. Peterson JJ, Orisme W, Fellows J, McDowell JH, Shelamer CL, Dugger DR, Smith WC (2005) A role for cytoskeletal elements in the light-driven translocation of proteins in rod photoreceptors. Invest. Opthalmol. Vis. Sci. 46: 3988-3998. PMC1578685
  4. Peterson JJ, Tam BM, Moritz OL, Shelamer CL, Dugger DR, McDowell JH, Hargrave PA, Papermaster DS, Smith WC (2003) Arrestin migrates in photoreceptors in response to light: A study of arrestin localization using an arrestin-GFP fusion protein in transgenic frogs. Exp. Eye Res. 76: 553-563.

photo of Dr Smith with test tubes

Alternative interaction partners for arrestin. Although arrestin is principally involved in the inactivation of the visual pigment to quench phototransduction, it is clear that arrestin interacts with other proteins in photoreceptors to mediate other processes. Our lab was the first to demonstrate an intersection between phototransduction and glycolysis, demonstrating that arrestin binds enolase1 in rod and cone photoreceptors. This interaction modulates glycolysis by 25% which is a significant fraction for cells that consume 108 ATP/sec, half of which is produced by glycolysis. This finding has served as the central area in the development of a new therapy for treating retinal degenerative diseases. In addition, we showed that arrestin also binds to one of the Bardet-Biedl Syndrome proteins (BBS5). This finding is redefining how we look at the ancestral ciliary structure of the photoreceptor, identifying it as an important reservoir for a pool of proteins with ready access to the outer segment disc region of rods and cones.

  1. Bolch SN, Dugger DR, Chong T, McDowell JH, Smith WC (2016) A splice variant of Bardet-Biedl Syndrome 5 (BBS5) protein that is selectively expressed in retina. PLoS ONE 11: e0148773.
  2. Smith TS, Spitzbarth B, Li J, Dugger DR, Stern-Schneider G, Sehn E, Bolch SN, McDowell JH, Tipton J, Wolfrum U, Smith WC (2013) Light-dependent phosphorylation of Bardet Biedl Syndrome 5 in photoreceptor cells modulates its interaction with arrestin1. Cell Mol Life Sci 70:4603-4616. PMC3819411
  3. Smith WC, Bolch SN, Dugger DR, Li J, Esquenazi I, Arendt A, Benzenhafer D, McDowell JH (2011) Interaction of arrestin with enolase1 in photoreceptors. Invest. Ophthalmol. Vis. Sci. 52(3):1832-40. PMC3101666

For a complete listing of publications please click here.

Opportunities for Undergraduate Research

Our laboratory is committed to providing research training experience for motivated undergraduates. Our philosophy is to provide the students with projects that are an integral part of our research program such that they make a significant contribution to our research goals. Many undergraduate projects are included in the publications from our lab. A minimum commitment of two consecutive semesters is required. If interested, please contact Clay Smith ( for more information.