Abstract
A 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 β subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.
Original language | English (US) |
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Pages (from-to) | 14117-14127 |
Number of pages | 11 |
Journal | Journal of Neuroscience |
Volume | 27 |
Issue number | 51 |
DOIs | |
State | Published - Dec 19 2007 |
Externally published | Yes |
Keywords
- G-protein
- Intracellular targeting
- Protein degradation
- RGS proteins
- Signal transduction
- Striatum
ASJC Scopus subject areas
- General Neuroscience