Research Interests:
Signaling via heterotrimeric G proteins crucially controls a wide range of neuronal processes such as neurotransmitter action, differentiation, excitability, sensory perception and many others. The research in our laboratory addresses molecular and cellular mechanisms that regulate the function of G proteins. In particular, we are interested in understanding intricate regulatory dynamics of G protein pathways in the following two systems.
- Basal ganglia where G proteins mediate reward behavior and movement coordination underlying not only addictive effects of abused drugs such as opioids and cocaine but also dysfunctions observed in movement disorders such as Parkinson's disease and dyskinesias.
- Retina where G protein signaling system of primary sensory neurons, photoreceptors generates response to light, a process indispensable for our ability to see.
Research directions in the laboratory include discovery and characterization of novel G protein regulators, delineation of protein-protein interactions, feedback mechanisms and logistics of signaling pathway organization. In our research we use a range of multidisciplinary approaches involving identification of components of signaling complex by proteomics approaches, measurement of protein functional activity by in vitro enzyme kinetics, analysis of synthesis, trafficking and degradation of signaling proteins in cell culture and establishment of transgenic mouse models with inactivated or altered components of G protein signaling machinery.
Selected Publications:
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Hooks S., Martemyanov K ., and Zachariou, V. (2008) A role of RGS proteins in drug addiction. Biochem. Pharmacol . 75 , 76-84
Cao Y., Song H., Okawa H., Sampath A.P., Sokolov M., Martemyanov K.A. (2008) Targeting of RGS7/G b 5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP. J.Neurosci . 28 , 10443 – 10449
Martemyanov K.A. , Krispel C.M., Lishko P.V., Burns M.E., Arshavsky V.Y. (2008) Functional comparison of RGS9 splice isoforms in a living cell. Proc. Natl. Acad. Sci. USA 105 , 20988 - 20993
Song JH, Song H, Wensel TG, Sokolov M, Martemyanov KA. Localization and differential interaction of R7 RGS proteins with their membrane anchors R7BP and R9AP in neurons of vertebrate retina. Mol Cell Neurosci. 2007 Jun;35(2):311-9.
Anderson G.R., Semenov A., Song J.H. and Martemyanov K.A. (2007) The membrane anchor R7BP controls the proteolytic stability of the striatal specific RGS protein, RGS9-2. J. Biol. Chem . 282 , 4772 (Featured as the Paper of the Week)
Grant, G.E., Guo, L.W., Vestling M.M., Martemyanov K.A . , Arshavsky V.Y. and Ruoho A.E. (2006) The N-terminus of GTP g S-activated transducin a -subunit interacts with the C-terminus of the cGMP phosphodiesterase g -subunit. J. Biol. Chem. 281 , 6194 - 6202
Song J.H., Wataaja J.J., Martemyanov K.A . (2006) Subcellular targeting of RGS9-2 is controlled by multiple molecular determinants on its membrane anchor, R7BP. J. Biol. Chem. 281 , 15361-15369.
Krispel C.M., Chen D., Melling N., Chen Y-J., Martemyanov K.A ., Quillinan N., Arshavsky V.Y., Wensel T.G., Chen C-K, and Burns M.E. (2006) RGS expression rate-limits recovery of rod photoresponses. Neuron 51 , 409-416 (Subject of a Neuron Minireview by E.N. Pugh)
Baker S.A. , Martemyanov K.A.* , Shavkunov A.S. and Arshavsky V.Y. (2006) Kinetic mechanism of RGS9-1 potentiation by R9AP. Biochemistry 45 , 10690-10697
Martemyanov K.A . , Yoo P.J ., Skiba N.P ., Arshavsky V.Y . (2005) R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. J. Biol. Chem. 280 , 5133-5136 (Accelerated publication) Guo L.W ., Hajipour A.R ., Gavala M.L ., Arbabian M ., Martemyanov K.A ., Arshavsky V.Y ., Ruoho A.E . (2005) Sulfhydryl-reactive, cleavable, and radioiodinatable benzophenone photoprobes for study of protein-protein interaction. Bioconjug. Chem. 16 , 685-693
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