Anderson, Garret R.Lujan, RafaelSemenov, ArthurPravetoni, MarcoPosokhova, Ekaterina N.Song, Joseph H.Uversky, VladimirChen, Ching-KangWickman, KevinMartemyanov, Kirill A.2019-10-162019-10-162007-12-19Anderson, G. R., Lujan, R., Semenov, A., Pravetoni, M., Posokhova, E. N., Song, J. H., … Martemyanov, K. A. (2007). Expression and localization of RGS9-2/G 5/R7BP complex in vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(51), 14117–14127. doi:10.1523/JNEUROSCI.3884-07.2007https://hdl.handle.net/1805/21182A member of regulator of G-protein signaling family, RGS9-2, is an essential modulator of signaling through neuronal dopamine and opioid G-protein-coupled receptors. Recent findings indicate that the abundance of RGS9-2 determines sensitivity of signaling in the locomotor and reward systems in the striatum. In this study we report the mechanism that sets the concentration of RGS9-2 in vivo, thus controlling G-protein signaling sensitivity in the region. We found that RGS9-2 possesses specific degradation determinants which target it for constitutive destruction by lysosomal cysteine proteases. Shielding of these determinants by the binding partner R7 binding-protein (R7BP) controls RGS9-2 expression at the posttranslational level. In addition, binding to R7BP in neurons targets RGS9-2 to the specific intracellular compartment, the postsynaptic density. Implementation of this mechanism throughout ontogenetic development ensures expression of RGS9-2/type 5 G-protein beta subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.en-USPublisher PolicyG-proteinSignal transductionRGS proteinsProtein degradationIntracellular targetingStriatumArticle