title: The mechanism of membrane-translocation of regulator of G-protein signaling (RGS) 8 induced by Galpha expression.
abstract: RGS (regulators of G-protein signaling) proteins comprise a large family that modulates heterotrimeric G-protein signaling. This protein family has a common RGS domain and functions as GTPase-activating proteins for the alpha-subunits of heterotrimeric G-proteins located at the plasma membrane. RGS8 was identified as a neuron-specific RGS protein, which belongs to the B/R4 subfamily. We previously showed that RGS8 protein was translocated to the plasma membrane from the nucleus on coexpression of GTPase-deficient Galphao (GalphaoQL). Here, we first examined which subtypes of Galpha can induce the translocation of RGS8. When the Galphai family was expressed, the translocation of RGS8 did occur. To investigate the mechanism of this translocation, we generated a mutant RGS8 with reduced affinity to Galphao and an RGS-insensitive (RGS-i) mutant of GalphaoQL. Co-expression experiments with both mutants revealed that disruption of the Galpha-RGS8 interaction abolished the membrane-translocation of RGS8 despite the apparent membrane localization of RGS-i GalphaoQL. These results demonstrated that RGS8 is recruited to the plasma membrane where G-proteins are activated mainly by direct association with Galpha.
authors.affiliation: Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Masuho
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Osamu
authors.initials: O
authors.lastname: Saitoh
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D044385:GTP-Binding Protein alpha Subunits / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D020710:RGS Proteins; C116924:RGS8 protein, human; C486485:Rgs8 protein, rat; D019206:GTP-Binding Protein alpha Subunits, Gi-Go