Kirill A. Martemyanov, Ph.D.
Associate Professor with Tenure
Ph.D., Institute of Protein Research, Russian Academy of Sciences, Molecular Biology, 2000
Department of Neuroscience
The Scripps Research Institute
130 Scripps Way C347
Jupiter, Florida 33458
The main emphasis of the research in the laboratory is on the fundamental principles that regulate signaling via G protein coupled receptors (GPCR). GPCRs mediate a vast variety of critical biological processes ranging from proliferation and motility to cellular reception and excitability. GPCR signaling pathways are of particular importance for the nervous system function where they control many fundamental processes including excitability, differentiation, sensory perception and synaptic transmission. Importantly, but not surprisingly, even subtle imbalances in GPCR signaling often lead to the most profound nervous system disorders ranging from blindness and cognitive problems to grave neurological diseases.
Specifically, our laboratory is interested in understanding intricate regulatory dynamics of G protein pathways in the following two neuronal 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, Huntington’s disease, Tourette syndrome and tardive dyskinesia.
- Retina where G protein signaling systems of primary sensory neurons, photoreceptors and downstream ON-bipolar cells act in tandem to generate responses to light and synaptically encode them to enable our vision. Dysfunctions in these processes are known to be leading causes of a range of ocular pathologies including macular degeneration and congenital night blindness.
Much of our current efforts are focused on a family of key regulators of GPCR signaling pathways, the Regulator of G protein Signaling (RGS) proteins. RGS proteins constitute a large family of proteins that promote G protein inactivation by facilitating their GTP hydrolysis thus ensuring timely inactivation of the GPCR responses. Many members of the RGS family have been clinically linked to human disease conditions that have been recapitulated in the genetic mouse models. Serving as a central control point in GPCR signaling cascades, RGS proteins hold great promises as targets for the drug development. This brings the major emphasis of our research on elucidating molecular and cellular mechanisms of RGS proteins function in cellular signaling in addition to the efforts to uncover novel regulatory principles.
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 complexes by proteomics, measurement of protein functional activity by in vitro enzyme kinetics, analysis of synthesis, trafficking and degradation of signaling proteins in cell culture and behavioral characterization of genetic mouse models with altered components of G protein signaling machinery.
Martemyanov K.A., Hopp J.A. and Arshavsky V.Y. (2003) Specificity of G protein-RGS protein recognition is regulated by affinity adapters. Neuron 38, 857-862
Hooks S., Martemyanov K., and Zachariou, V. (2008) A role of RGS proteins in drug addiction. Biochem. Pharmacol. 75, 76-84
Anderson G.R., Cao Y., Davidson S., Truong H.V., Pravetoni M., Thomas M., Wickman K., Giesler G.J.Jr., Martemyanov K.A. (2010) R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor learning and locomotor responses to cocaine. Neuropsychopharmacology 35, 1040-1050
Roloff A.M., Anderson G.R., Martemyanov K.A., Thayer S.A. (2010) Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity. J. Neurosci. 30, 3072-3081
Xie K., Allen K.L., Kourrich S., Colón-Saez J., Thomas, M.J., Wickman K., Martemyanov K.A. (2010) Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nature Neuroscience 13, 661-663
Cao Y., Posokhova E., Martemyanov K.A. (2011) TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6 dependent manner. J. Neurosci. 31, 11521-11526.
Xie K., Martemyanov K.A. (2011) Control of striatal signaling by G protein regulators. Front. Neuroanat. 5, 49
Cao Y., Pahlberg J., Sarria I., Kamasawa N., Sampath A.P., Martemyanov K.A. (2012) Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proc. Natl. Acad. Sci. USA109, 7905-7910
Orlandi C., Posokhova E., Masuho I., Ray T.A., Hasan N., Gregg R.G., Martemyanov K.A. (2012) GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes. J. Cell Biol. 197, 711-719
Xie K., Masuho I., Brand C., Dessauer C.W., Martemyanov K.A. (2012) The Complex of G Protein Regulator RGS9-2 and Gβ5 Controls Sensitization and Signaling Kinetics of Type 5 Adenylyl Cyclase in the Striatum. Science Signaling 239, ra63
For the complete list of publications please visit PubMed.
Awards, Recognition, Appointments, and Honors
1998 European Academy Prize in Biology
1999 Russian Biochemical Society Award
2002 American Heart Association Fellowship
2004 Knights Templar Foundation Award
2008 McKnight Land-Grant Professorship
2009 NIDA Independent Scientist Award
2014 ARVO Cogan Award