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Synergetic Effect of Recoverin and Calmodulin on Regulation of Rhodopsin Kinase

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Synergetic Effect of Recoverin and Calmodulin on Regulation of Rhodopsin Kinase Thomas Jefferson University Jefferson Digital Commons Department of Biochemistry and Molecular Department of Biochemistry and Molecular Biology Faculty Papers Biology 1-1-2012 Synergetic effect of recoverin and calmodulin on regulation of rhodopsin kinase. Ilya I Grigoriev Lomonosov Moscow State University Ivan I Senin Lomonosov Moscow State University Natalya K Tikhomirova Lomonosov Moscow State University Konstantin E Komolov Lomonosov Moscow State University; University of Oldenburg, Oldenburg, Germany; Department of FBiochemistrollow this andy and additional Molecular works Biology at: ,https:/ Thomas/jdc.jeff Jeffersonerson.edu/bmpfp University Ser geiPar tE of P theermy Medicalakov Biochemistry Commons, and the Medical Molecular Biology Commons LetInstitute us for knowBiological Instrumentationhow access of the tRussiano this Academy document of Sciences benefits ouy RecommendedSee next page for Citation additional authors Grigoriev, Ilya I; Senin, Ivan I; Tikhomirova, Natalya K; Komolov, Konstantin E; Permyakov, Sergei E; Zernii, Evgeni Yu; Koch, Karl-Wilhelm; and Philippov, Pavel P, "Synergetic effect of recoverin and calmodulin on regulation of rhodopsin kinase." (2012). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 36. https://jdc.jefferson.edu/bmpfp/36 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Department of Biochemistry and Molecular Biology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Authors Ilya I Grigoriev, Ivan I Senin, Natalya K Tikhomirova, Konstantin E Komolov, Sergei E Permyakov, Evgeni Yu Zernii, Karl-Wilhelm Koch, and Pavel P Philippov This article is available at Jefferson Digital Commons: https://jdc.jefferson.edu/bmpfp/36 ORIGINAL RESEARCH ARTICLE published: 08 March 2012 MOLECULAR NEUROSCIENCE doi: 10.3389/fnmol.2012.00028 Synergetic effect of recoverin and calmodulin on regulation of rhodopsin kinase Ilya I. Grigoriev 1, Ivan I. Senin1*, Natalya K.Tikhomirova1, Konstantin E. Komolov 1,2†, Sergei E. Permyakov 3, EvgeniYu. Zernii 1*, Karl-Wilhelm Koch2 and Pavel P.Philippov 1 1 Department of Cell Signaling, A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia 2 Biochemistry Group, Department of Biology and Environmental Sciences, University of Oldenburg, Oldenburg, Germany 3 Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow Region, Russia Edited by: Phosphorylation of photoactivated rhodopsin by rhodopsin kinase (RK or GRK1), a first step Michael R. Kreutz, Leibniz-Institute for of the phototransduction cascade turnoff, is under the control of Ca2+/recoverin. Here, we Neurobiology, Germany demonstrate that calmodulin, a ubiquitous Ca2+-sensor, can inhibit RK, though less effec- Reviewed by: Karl Heinz Braunewell, Southern tively than recoverin does. We have utilized the surface plasmon resonance technology to Research Institute, USA map the calmodulin binding site in the RK molecule. Calmodulin does not interact with Jacques Haiech, University of the recoverin-binding site within amino acid residues M1-S25 of the enzyme. Instead, the Strasbourg, France high affinity calmodulin binding site is localized within a stretch of amino acid residues *Correspondence: V150-K175 in the N-terminal regulatory region of RK. Moreover, the inhibitory effect of Ivan I. Senin and Evgeni Yu. Zernii, Department of Cell Signaling, A.N. calmodulin and recoverin on RK activity is synergetic, which is in agreement with the exis- 2+ Belozersky Institute of tence of separate binding sites for each Ca -sensing protein. The synergetic inhibition Physico-Chemical Biology, of RK by both Ca2+-sensors occurs over a broader range of Ca2+-concentration than by Lomonosov Moscow State recoverin alone, indicating increased Ca2+-sensitivity of RK regulation in the presence of University, Leninskie Gory 1, Building 2+ 40, Moscow 119992, Russia. both Ca -sensors. Taken together, our data suggest that RK regulation by calmodulin in e-mail: [email protected]; photoreceptor cells could complement the well-known inhibitory effect of recoverin on RK. [email protected] Keywords: rhodopsin kinase, calmodulin, recoverin, phosphorylation, surface plasmon resonance †Present address: Konstantin E. Komolov, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. INTRODUCTION The concentration of calmodulin in neurons (including rod outer Key aspects of the neuronal activity from neurotransmission to segments, ROS) is normally 10–25 μM(Liebman, 1972; Kohnken gene expression are regulated by changes in the intracellular free et al., 1981; Kakiuchi et al., 1982) and is comparable to the level calcium concentration. Effects of calcium on various processes in of NCS family proteins (maximum intracellular concentration of the cell are mediated by Ca2+ sensor proteins. The important prop- 30–40 μM was observed in the case of hippocalcin in hippocam- erty of these proteins is the ability to change their conformation pal neurons and recoverin in photoreceptors; Klenchin et al., 1995; upon Ca2+-binding, thereby transmitting the signal to the effector McCue et al., 2010; Mikhaylova et al., 2011). In this case, one of enzymes. The effects of calcium in different cells of the most tissues the possible mechanisms underlying the effective functioning of are mediated primarily by ubiquitous calcium sensor calmodulin the NCSs is based on the different affinities of NCSs and calmod- (Hoeflich and Ikura, 2002), belonging to the large group of EF- ulin to calcium. This is for example realized when calmodulin and hand calcium-binding proteins. In addition to calmodulin, the NCS proteins regulate a specific target protein in different ranges other EF-hand calcium-sensitive proteins of the neuronal calcium of cytoplasmic calcium (for review, see Burgoyne, 2007; McCue sensor (NCS) and caldendrin/calneuron families are expressed in et al., 2010). neurons (McCue et al., 2010). These proteins regulate different In addition to competitive regulation based on the variable aspects of neuronal function including neurotransmitter release, Ca2+-sensitivity, the effective functioning of NCSs, and calmod- channel and receptor regulation, control of gene transcription, ulin can be implemented through their interaction with target neuronal growth,and survival. NCS proteins provide a fine-tuning proteins using separate binding sites. The examples of simul- of regulatory mechanisms triggered by changes in calcium level taneous regulation of the effector enzymes by several Ca2+- in neurons while calmodulin operates more as an universal sen- binding proteins are quite common. In photoreceptor cells, reti- sor of calcium signals. Some of the protein targets are common nal guanylyl cyclase 1 contains independent binding sites for for both calmodulin and NCS proteins and in a number of cases four Ca2+-binding proteins: guanylyl cyclase activating protein they were shown to compete for the same binding sites in target 1 (GCAP1; Lange et al., 1999), GCAP2 (Duda et al., 2005), S100B molecules (Schaad et al.,1996; Haynes et al.,2006; Few et al.,2011). (Duda et al., 2002), and neurocalcin (Venkataraman et al., 2008). Frontiers in Molecular Neuroscience www.frontiersin.org March 2012 | Volume 5 | Article 28 | 1 Grigoriev et al. Rhodopsin kinase regulation by calmodulin and recoverin 2+ Four Ca binding EF-hand proteins are involved in regula- (K D) of recoverin–RK complex is about 6 μM(Satpaev et al., tion of sodium/proton exchanger 1 (NHE) via different sites on 1998). The half-maximal inhibition of rhodopsin phosphorylation 2+ either juxtamembrane region of NHE1 (calcineurin homologous occurs at 3–6 μM recoverin and at 1.5–3 μM[Ca ]free (Klenchin proteins 1, 2, and tescalcin) or C-terminal regulatory domain et al., 1995; Senin et al., 1997; Weiergräber et al., 2006; Zernii et al., (calmodulin; Köster et al., 2011). Another example includes Ca2+- 2011). dependent regulation of chimeric calmodulin-dependent protein While retina-specific GRK1 (RK) and GRK7 are regulated by kinase from plants (Sathyanarayanan et al., 2000). This enzyme Ca2+/recoverin, other GRKs (GRK2-6) are found to be inhibited contains visinin-like domain, which serves as an intramolecu- by the universal mediator of Ca2+ signaling calmodulin (Chuang lar NCS-like regulator. Such a structure allows the enzyme to et al., 1996; Pronin et al., 1997). It was shown that calmodulin complement the external regulation of its activity by calmod- binding sites in GRK2 and GRK5 are located at both the N- and ulin with intramolecular regulation utilizing the visinin-like C-terminal regions of their RH domains and seem to be indepen- domain. dent (Levay et al., 1998). Another report suggests that the activity Recoverin is an NCS protein that is primarily expressed in of RK can be regulated not only by recoverin, but also
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