Research Summary Arrestin Protein 2

photo Dr Smith Research to Prevent Blindness Foundation

Mechanism 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.