Kirill Martemyanov Massachusetts Eye and Ear Infirmary 243 Charles St. Boston, MA 02467 Tel.: (617) 573-3111 E-Mail: kirill_martemyanov@meei.harvard.edu Laboratory webpage Sponsor: Vadim Arshavsky vadim_arshavsky@meei.harvard.edu

"The Molecular Bases of Eye Diseases training program at Harvard Medical School provided me with a splendid opportunity to dive into the heart of vision research and to meet interesting people"

Photoreceptor cells are sensory neurons responsible for the detection and primary processing of information entering the eye in the form of photons of light. The basic functions of photoreceptors are to capture photons, to generate a second messenger signal, to translate this signal into a change in electrical activity and, finally, to transmit this information to the secondary neurons in the retina through synaptic release. Photoreceptors transmit the light stimulus via G protein based signal transduction pathway called phototransduction cascade. In this cascade, the heterotrimeric G protein, transducin, becomes activated by photoexcited rhodopsin, and its GTP-bound a subunit, Ga_t, interacts with the effector Ø the g subunit of cGMP phosphodiesterase (PDEg). This interaction releases the inhibitory constraint that PDE g imposes on the PDE catalytic subunits leading to the stimulation of PDE activity. The signal is terminated when the photoreceptor-specific RGS, the complex between RGS9-1 and type 5 G protein b subunit (RGS9-1 x Gb5L), binds to transducin and activates its GTPase activity. This is followed by transducin dissociation from PDEg and the return of PDE to its inactive state. Our current research is aimed at defining the role of each individual protein subunit of the entire GTPase activating complex in regulating its catalytic activity and substrate specificity.

Publications

Skiba N.P., Martemyanov K.A., Elfenbein A., Hopp J.A., Bohm A., Simonds W.F., Arshavsky V.Y. (2001) RGS9-Gb5 substrate selectivity in photoreceptors: opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex. J. Biol. Chem. 276, 37365-37372

Lishko P.V., Martemyanov K.A., Hopp J.A., Arshavsky V.Y. (2002) Specific Binding of RGS9-Gbeta 5L to Protein Anchor in Photoreceptor Membranes Greatly Enhances Its Catalytic Activity. J. Biol. Chem. 277, 24376-24381

Martemyanov K.A. and Arshavsky V.Y. (2002) Noncatalytic domains of RGS9-1∙Gb5L play a decisive role in establishing its substrate specificity. J. Biol. Chem. 277,in press.

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Last updated: October 28, 2002