title: Differential localization of G protein βγ subunits.
abstract: G protein βγ subunits play essential roles in regulating cellular signaling cascades, yet little is known about their distribution in tissues or their subcellular localization. While previous studies have suggested specific isoforms may exhibit a wide range of distributions throughout the central nervous system, a thorough investigation of the expression patterns of both Gβ and Gγ isoforms within subcellular fractions has not been conducted. To address this, we applied a targeted proteomics approach known as multiple-reaction monitoring to analyze localization patterns of Gβ and Gγ isoforms in pre- and postsynaptic fractions isolated from cortex, cerebellum, hippocampus, and striatum. Particular Gβ and Gγ subunits were found to exhibit distinct regional and subcellular localization patterns throughout the brain. Significant differences in subcellular localization between pre- and postsynaptic fractions were observed within the striatum for most Gβ and Gγ isoforms, while others exhibited completely unique expression patterns in all four brain regions examined. Such differences are a prerequisite for understanding roles of individual subunits in regulating specific signaling pathways throughout the central nervous system.
authors.affiliation: Department of Pharmacology, ‡Mass Spectrometry Research Center, §Department of Molecular Physiology and Biophysics, and ∥Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232-6600, United States.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Betke
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.forename: David B
authors.initials: DB
authors.lastname: Friedman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baucum
authors.forename: Karren
authors.initials: K
authors.lastname: Hyde
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Schey
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020033:Protein Isoforms