Rick Cote, Ph.D.

Rick Cote, Ph.D.

MCBS Department Chair

Educational Background:

 Postdoc., University of Wisconsin-Madison, 1981-1985
 Ph.D., University of Wisconsin-Madison, 1974-1980
 B.S., Tufts University, 1970-1974

General Area of Interest and/or Speciality:

 Signal Transduction in Neuronal Cells

Research Activities:

National Eye Institute (NIH), “Role of cGMP in Photoreceptor Function"
United States Department of Agriculture, “Nucleotide metabolism during signal transduction in retinal photoreceptor cells”

Courses Taught:

General Biochemistry Lab BCHM 659; Advanced Topic BCHM 960; Protein Structure & Function BCHM 794; Lab Biochem & Molecular Biology BCHM 755; Investigations BCHM 795; Senior Thesis BCHM 799

Publications:

Zeng-Elmore, X., Gao, X.Z., Pellarin, R., Schneidman-Duhovny, D., Zhang, X.J., Kozacka, K.A., Tang,Y., Sali, A., Chalkley, R.J., Cote, R.H., and Chu,F. (2014). Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling. J. Mol. Biol. 426, 3713-3728.

Cahill, K.B., Quade, J.H., Carleton, K.L., and Cote, R.H. (2012). Identification of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6. J. Biol. Chem. 287, 41406-41416.

Matte, S.L., Laue, T.M., and Cote, R.H. (2012). Characterization of the conformational changes and protein-protein interactions of the rod photoreceptor phosphodiesterase (PDE6). J. Biol. Chem. 287, 20111-20121.

Zhang, X.J., Gao, X.Z., Yao, W., and Cote, R.H. (2012). Functional mapping of interacting regions of the photoreceptor phosphodiesterase (PDE6) g-subunit with PDE6 catalytic dimer, transducin, and Regulator of G-protein Signaling9-1 (RGS9-1). J. Biol. Chem. 287 , 26312-26320.

Cahill, K. B. and Cote, R. H. Phosphodiesterase 6C, cGMP-specific cone a'. UCSD-Nature Molecule Pages doi:10.1038/mp.a001756.01. 2011.

Gitschier, H. J. and Cote, R. H. Phosphodiesterase 6D, cGMP-specific rod d. UCSD-Nature Molecule Pages doi:10.1038/mp.a001757.01. 2011.

Zhang, X. J. and Cote, R. H. Pde6H, cone-specific inhibitory subunit of cone PDE6. UCSD-Nature Molecule Pages doi:10.1038/mp.a001758.01. 2011.

Cote, R.H. and Cahill, K.B. (2010). Function and regulation of photoreceptor phosphodiesterase (PDE6) in the visual signaling pathway. In Handbook of Cell Signaling, R.Bradshaw and E.Dennis, eds. (San Diego: Elsevier), pp. 1445-1451.

X.J. Zhang, Skiba, N.P., and Cote, R.H. (2010). Structural requirements of the photoreceptor phosphodiesterase γ-subunit for inhibition of rod PDE6 holoenzyme and for its activation by transducin. J.Biol.Chem. in press

Liu,Y., Matte, S., Corbin, J., Francis, S., and Cote, R.H. (2009). Probing the catalytic sites and activation mechanism of photoreceptor phosphodiesterase (PDE6) using radiolabeled PDE inhibitors. J Biol. Chem. 284, 31541-31547

Cote, R.H. and Cahill, K.B. (2009). Function and regulation of photoreceptor phosphodiesterase (PDE6) in the visual signaling pathway. In Handbook of Cell Signaling, R.Bradshaw and E.Dennis, eds. (San Diego: Elsevier), pp. 1445-1451

Zhang, X.J., Cahill, K.B., Elfenbein, A., Arshavsky, V.Y., Cote, R.H. (2008). Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol. Chem. 283, 29699-29705

Cote, R.H. (2008). The cGMP signaling pathway in retinal photoreceptors and the central role of photoreceptor phosphodiesterase (PDE6). In Visual Transduction and Non-Visual Light Perception, J.Tombran-Tink and C.J.Barnstable, eds. (Totawa: Humana Press), pp. 141-169.

Cote, R.H. (2006). Photoreceptor phosphodiesterase (PDE6): a G-protein-activated PDE regulating visual excitation in rod and cone photoreceptor cells. In Cyclic Nucleotide Phosphodiesterases in Health and Disease, J.A.Beavo, S.H.Francis, and M.D.Houslay, eds. (Boca Raton , FL : CRC Press), pp. 165-193.

Pentia, D., Hosier, S., and Cote, R.H. (2006). The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties. J Biol. Chem. 281: 5500-5505

Zhang, X., Feng, Q., and Cote, R.H. (2005). Efficacy and selectivity of phosphodiesterase-targeted drugs in inhibiting photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors. Invest. Ophthalmol. Vis. Sci. 46 , 3060-3066.

Zhang, H., Hosier, S., Terew, J.M., Zhang, K., Cote, R.H., and Baehr,W. (2005). Assay and functional properties of PrBP (PDEd), a prenyl binding protein interacting with multiple partners. Methods Enzymol. 403: 42-56.

Cote, R.H. (2005). Cyclic guanosine 5'-monophosphate binding to the regulatory GAF domains of photoreceptor phosphodiesterase (PDE6). Methods in Molecular Biology 307 , 141-154.

Pentia, D.C., Hosier, S., Collupy, R.A., Valeriani, B.A., and Cote, R.H. (2005). Purification of PDE6 isozymes from mammalian retina. Methods in Molecular Biology 307: 125-140.

Carleton, K.L., Spady, T.C., and Cote, R.H. (2005). Rod and cone opsin families differ in spectral tuning domains but not signal transducing domains as judged by saturated evolutionary trace analysis. J. Mol. Evol. 61: 75-89

Zhang, X. and Cote, R.H. (2005) cGMP signaling in vertebrate retinal photoreceptor cells. Front. Bioscience 10:1191-1204

Norton A.W., Hosier, S., Terew, J.M., Li, N., Dhingra, A., Vardi, N., Baehr, W., and Cote, R.H. (2005). Evaluation of the 17 kDa prenyl binding protein as a regulatory protein for phototransduction in retinal photoreceptors. J Biol Chem. 280: 1248-1256.

Cote , R.H. (2004). Characteristics of Photoreceptor PDE (PDE6): similarities and differences to PDE5. Intl. J. Impotence Res. 16, S28-S33.

Corbin, J.D., Kotera, J., Gopal, V.K., Cote, R.H., and Francis, S.H. (2003). Regulation of cyclic nucleotide levels by sequestration. In Handbook of Cell Signaling, R. Bradshaw and E. Dennis, eds. (San Diego: Academic Press), pp. 453-457.

Cote, R. H. (2003). Structure, function, and regulation of photoreceptor phosphodiesterase (PDE6). In Handbook of Cell Signaling, R. A. Bradshaw and E. A. Dennis, eds. (San Diego: Academic Press), pp. 453-458.

Paglia, M.J., Mou, H., and Cote, R.H. (2002). Regulation of photoreceptor phosphodiesterase (PDE6) by phosphorylation of its inhibitory γ subunit re-evaluated. J. Biol. Chem. 277, 5017-5023.

Kameni Tcheudji, J.F., Lebeau, L., Virmaux, N., Maftei, C.G., Cote, R.H., Lugnier, C., and Schultz, P. (2001). Molecular organization of bovine rod cGMP-phosphodiesterase 6. J. Mol. Biol. 310, 781-791.

Mou, H. and Cote, R.H. (2001). The catalytic and GAF domains of the rod cGMP phosphodiesterase (PDE6) heterodimer are regulated by distinct regions of its inhibitory γ subunit. J. Biol. Chem. 276, 27527-27534.

Cote, R.H. (2000). Kinetics and regulation of cGMP binding to noncatalytic binding sites on photoreceptor phosphodiesterase. Methods Enzymol. 315, 646-672.

Norton, A.W., D'Amours, M.R., Grazio, H.J., Hebert, T.L., and Cote, R.H. (2000). Mechanism of transducin activation of frog rod photoreceptor phosphodiesterase: allosteric interactions between the inhibitory γ subunit and the noncatalytic cGMP binding sites. J. Biol. Chem. 275, 38611-38619.

D'Amours, M.R. and Cote, R.H. (1999). Regulation of photoreceptor phosphodiesterase catalysis by its noncatalytic cGMP binding sites. Biochem. J. 340, 863-869.

D'Amours, M.R., Granovsky, A.E., Artemyev, N.O., and Cote, R.H. (1999). The potency and mechanism of action of E4021, a PDE5-selective inhibitor, on the photoreceptor phosphodiesterase depends on its state of activation. Mol. Pharmacol. 55, 508-514.

Mou, H., Grazio, H.J., Cook, T.A., Beavo, J.A., and Cote, R.H. (1999). cGMP binding to noncatalytic sites on mammalian rod photoreceptor phosphodiesterase is regulated by binding of its γ and δ subunits. J. Biol. Chem. 274, 18813-18820.

Artemyev, N.O., Arshavsky, V.Y., and Cote, R.H. (1998). Photoreceptor phosphodiesterase: Interaction of inhibitory γ subunit and cyclic GMP with specific binding sites on catalytic subunits. Methods 14, 93-104.

Hebert, M.C., Schwede, F., Jastorff, B., and Cote, R.H. (1998). Structural features of the noncatalytic cGMP binding sites of frog photoreceptor phosphodiesterase using cGMP analogs. J. Biol. Chem. 273, 5557-5565.

Coccia, V.J. and Cote, R.H. (1994). Regulation of intracellular cyclic GMP concentration by light and calcium in electropermeabilized rod photoreceptors. J. Gen. Physiol. 103, 67-86.

Cote, R.H., Bownds, M.D., and Arshavsky, V.Y. (1994). cGMP binding sites on photoreceptor phosphodiesterase: Role in feedback regulation of visual transduction. Proc. Natl. Acad. Sci. U.S.A. 91, 4845-4849.

Cote, R.H. and Brunnock, M.A. (1993). Intracellular cGMP concentration in rod photoreceptors is regulated by binding to high and moderate affinity cGMP binding sites. J. Biol. Chem. 268, 17190-17198.

Forget, R.S., Martin, J.E., and Cote, R.H. (1993). A centrifugal separation procedure detects moderate affinity cGMP binding sites in membrane-associated proteins and permeabilized cells. Anal. Biochem. 215, 159-161.

Lisman, J.E., Erickson, M., Richard, E.A., Cote, R.H., Bacigalupo, J., Johnson, E.C., and Kirkwood, A. (1992). Mechanisms of amplification, deactivation and noise reduction in invertebrate photoreceptors. In Sensory Transduction, D. P. Corey and S. D. Roper, eds. (New York: Rockefeller Press), pp. 176-199.

Peer Reviewed Papers or Book Chapters:

  • Cote, R.H. and Cahill, K.B. (2009). Function and regulation of photoreceptor phosphodiesterase (PDE6) in the visual signaling pathway. In Handbook of Cell Signaling, R.Bradshaw and E.Dennis, eds. (San Diego: Elsevier), p. in press.
  • Liu, Y.T., Matte, S.L., Corbin, J.D., Francis, S.H., and Cote, R.H. (2009). Probing the catalytic sites and activation mechanism of photoreceptor phosphodiesterase (PDE6) using radiolabeled PDE inhibitors. J. Biol. Chem.  submitted.
  • Cote, R.H. (2008). The cGMP signaling pathway in retinal photoreceptors and the central role of photoreceptor phosphodiesterase (PDE6). In Visual Transduction and Non-Visual Light Perception, J.Tombran-Tink and C.J.Barnstable, eds. (Totawa: Humana Press), pp. 141-169.
  • Zhang, X.J., Cahill, K.B., Elfenbein, A., Arshavsky, V.Y., and Cote, R.H. (2008). Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J. Biol. Chem. 283, 29699-29705.

Major Presentations at Professional Meeting:

  • Invited speaker, Gordon Conference on Cyclic Nucleotide Phosphodiesterases in Il Ciocco, Italy, June 9-13, 2008. Topic: Allosteric regulation of PDE6.
Rick Cote
Rudman Hall, Rooms 379
Durham, NH 03824
Phone: 
(603) 862-2458