Kirill A. Martemyanov, Ph.D.
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.
Wang, Y., Fehlhaber, K.E., Sarria, I., Cao, Y., Ingram, N.T., Guerrero-Given, D., Throesch, B., Baldwin, K., Kamasawa, N., Ohtsuka, T., Sampath, A.P., Martemyanov, K.A. (2017) The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors. Neuron 93, 1359-1374.
Lohmann, K., Masuho, I., Patil, D.N., Baumann, H., Hebert, E., Steinrücke, S., Trujillano, D., Skamangas, N.K., Dobricic, V., Hüning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Münchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K.A. (2017) Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans. Hum Mol Genet. doi: 10.1093/hmg/ddx018.
Xie, K., Colgan, L.A., Dao, M.T., Muntean, B.S., Sutton, L.P., Orlandi, C., Boye, S.L., Boye, S.E., Shih, C.C., Li, Y., Xu, B., Smith, R.G., Yasuda, R., Martemyanov, K.A. (2016) NF1 is a direct protein effector essential for opioid signaling to Ras in the striatum. Curr. Biol. 26, 2992-3003.
Sutton L.P., Ostrovskaya O., Xie K., Orlandi C., Dao M., Wee S. and Martemyanov K.A. (2015) RGS7 regulates reward behavior by controlling opioid signaling in the striatum. Biol. Psych., 80, 235-245.
Masuho I., Kramer G.M., Ostrovskaya O., Jones C.D. and Martemyanov K.A. (2015) Fingerprinting catalytic activity of GPCRs on exhaustive set of G protein substrates reveals complex profiles of functional bias. Science Signaling, 8(405):ra123.
Xie K., Masuho I., Shih C.C., Sasaki K., Lai C.W., Han P.L., Ueda H., Dessauer C.W., Ehrlich M.E., Xu B., Willardson B.M. Martemyanov K.A. (2015) Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling. eLife, e10451
Cao Y., Sarria I., Fehlhaber K.E., Kamasawa N., Orlandi C., James K.N., Hazen J.L., Gardner M.R., Farzan M., Lee A., Baker S.A., Baldwin K., Sampath A.P. and Martemyanov K.A. (2015) Mechanisms for selective synaptic wiring of rod photoreceptors into the retinal circuitry and its role in vision. Neuron, 87, 1248-1260.
Sarria I., Pahlberg J., Cao Y., Kolesnikov A.V., Kefalov V.J., Sampath A.P., Martemyanov K.A. (2015) Sensitivity and kinetics of synaptic transmission between photoreceptor and ON-bipolar neurons differentially impact visually-guided behavior. eLife, e06358.
Ostrovskaya O., Xie K., Masuho I., Fajardo-Serrano A., Lujan R., Wickman K., Martemyanov K.A. (2014) RGS7/Gb5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling., eLife, e02053.
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