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.
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 beta subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.
Anderson
Garret R
GR
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Lujan
Rafael
R
Semenov
Arthur
A
Pravetoni
Marco
M
Posokhova
Ekaterina N
EN
Song
Joseph H
JH
Uversky
Vladimir
V
Chen
Ching-Kang
CK
Wickman
Kevin
K
Martemyanov
Kirill A
KA
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020710:RGS Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
C499440:R7BP protein, mouse; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D003546:Cysteine Endopeptidases