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Proc Natl Acad Sci U S A
1997 Aug 05;9416:8866-71. doi: 10.1073/pnas.94.16.8866.
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Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors.
Qin N, Platano D, Olcese R, Stefani E, Birnbaumer L.
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Several classes of voltage-gated Ca2+ channels (VGCCs) are inhibited by G proteins activated by receptors for neurotransmitters and neuromodulatory peptides. Evidence has accumulated to indicate that for non-L-type Ca2+ channels the executing arm of the activated G protein is its betagamma dimer (Gbetagamma). We report below the existence of two Gbetagamma-binding sites on the A-, B-, and E-type alpha1 subunits that form non-L-type Ca2+ channels. One, reported previously, is in loop 1 connecting transmembrane domains I and II. The second is located approximately in the middle of the ca. 600-aa-long C-terminal tails. Both Gbetagamma-binding regions also bind the Ca2+ channel beta subunit (CCbeta), which, when overexpressed, interferes with inhibition by activated G proteins. Replacement in alpha1E of loop 1 with that of the G protein-insensitive and Gbetagamma-binding-negative loop 1 of alpha1C did not abolish inhibition by G proteins, but the exchange of the alpha1E C terminus with that of alpha1C did. This and properties of alpha1E C-terminal truncations indicated that the Gbetagamma-binding site mediating the inhibition of Ca2+ channel activity is the one in the C terminus. Binding of Gbetagamma to this site was inhibited by an alpha1-binding domain of CCbeta, thus providing an explanation for the functional antagonism existing between CCbeta and G protein inhibition. The data do not support proposals that Gbetagamma inhibits alpha1 function by interacting with the site located in the loop I-II linker. These results define the molecular mechanism by which presynaptic G protein-coupled receptors inhibit neurotransmission.
Arbilla,
Morphine and beta-endorphin inhibit release of noradrenaline from cerebral cortex but not of dopamine from rat striatum.
1978, Pubmed
Arbilla,
Morphine and beta-endorphin inhibit release of noradrenaline from cerebral cortex but not of dopamine from rat striatum.
1978,
Pubmed Armstrong,
An enzymatic mechanism for potassium channel stimulation through pertussis-toxin-sensitive G proteins.
1992,
Pubmed Bean,
Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence.
1989,
Pubmed Birnbaumer,
The naming of voltage-gated calcium channels.
1994,
Pubmed Bourinet,
Determinants of the G protein-dependent opioid modulation of neuronal calcium channels.
1996,
Pubmed
,
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Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta-subunit in rat neurones.
1995,
Pubmed Chen,
A region of adenylyl cyclase 2 critical for regulation by G protein beta gamma subunits.
1995,
Pubmed Chen,
G(o)-2 protein mediates the reduction in Ca2+ currents by somatostatin in cultured ovine somatotrophs.
1996,
Pubmed Codina,
Purification of Ns and Ni, the coupling proteins of hormone-sensitive adenylyl cyclases without intervention of activating regulatory ligands.
1985,
Pubmed Codina,
Requirement for intramolecular domain interaction in activation of G protein alpha subunit by aluminum fluoride and GDP but not by GTP gamma S.
1994,
Pubmed De Waard,
Ca2+ channel regulation by a conserved beta subunit domain.
1994,
Pubmed
,
Xenbase De Waard,
Direct binding of G-protein betagamma complex to voltage-dependent calcium channels.
1997,
Pubmed
,
Xenbase Dolezal,
Effects of Pertussis Toxin Suggest a Role for G-Proteins in the Inhibition of Acetylcholine Release from Rat Myenteric Plexus by Opioid and Presynaptic Muscarinic Receptors.
1989,
Pubmed Dolphin,
Facilitation of Ca2+ current in excitable cells.
1996,
Pubmed Dunlap,
Exocytotic Ca2+ channels in mammalian central neurons.
1995,
Pubmed Dunlap,
Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones.
1981,
Pubmed Grassi,
Voltage-dependent GABA-induced modulation of calcium currents in chick sensory neurons.
1989,
Pubmed Herlitze,
Modulation of Ca2+ channels by G-protein beta gamma subunits.
1996,
Pubmed Herlitze,
Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel alpha1A subunit.
1997,
Pubmed Ikeda,
Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits.
1996,
Pubmed Kaneko,
Ca2+ channel inhibition by kappa opioid receptors expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Kleuss,
Different beta-subunits determine G-protein interaction with transmembrane receptors.
1992,
Pubmed Langer,
Physiological significance of alpha-adrenoceptor-mediated negative feedback mechanism regulating noradrenaline release during nerve stimulation.
1977,
Pubmed Langer,
Noradrenaline release from isolated muscles of the nictitating membrane of the cat.
1971,
Pubmed Lipscombe,
Alpha-adrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium-channel gating.
1989,
Pubmed Marchetti,
Effects of dopamine and noradrenaline on Ca channels of cultured sensory and sympathetic neurons of chick.
1986,
Pubmed McAllister-Williams,
The modulation of calcium channel currents recorded from adult rat dorsal raphe neurones by 5-HT1A receptor or direct G-protein activation.
1995,
Pubmed Neely,
Ca(2+)-dependent inactivation of a cloned cardiac Ca2+ channel alpha 1 subunit (alpha 1C) expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Noceti,
Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels.
1996,
Pubmed
,
Xenbase Olcese,
The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation.
1994,
Pubmed
,
Xenbase Peralta,
Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.
1987,
Pubmed Perez-Reyes,
Molecular biology of calcium channels.
1995,
Pubmed Perez-Reyes,
Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel.
1992,
Pubmed
,
Xenbase Pollo,
Voltage-dependent noradrenergic modulation of omega-conotoxin-sensitive Ca2+ channels in human neuroblastoma IMR32 cells.
1992,
Pubmed Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed Roche,
Abolition of G protein inhibition of alpha 1A and alpha 1B calcium channels by co-expression of the beta 3 subunit.
1995,
Pubmed
,
Xenbase Sanford,
Gamma-subunits of G proteins, but not their alpha- or beta-subunits, are polyisoprenylated. Studies on post-translational modifications using in vitro translation with rabbit reticulocyte lysates.
1991,
Pubmed Schneider,
G protein interaction with K+ and Ca2+ channels.
1997,
Pubmed
,
Xenbase Schneider,
Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit.
1994,
Pubmed
,
Xenbase Seward,
Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current.
1991,
Pubmed Taglialatela,
Novel voltage clamp to record small, fast currents from ion channels expressed in Xenopus oocytes.
1992,
Pubmed
,
Xenbase Tareilus,
A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit.
1997,
Pubmed
,
Xenbase Tsunoo,
Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.
1986,
Pubmed Valenzuela,
G alpha(o) is necessary for muscarinic regulation of Ca2+ channels in mouse heart.
1997,
Pubmed VanDongen,
Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go.
1988,
Pubmed Wei,
Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels.
1991,
Pubmed
,
Xenbase Wei,
Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac alpha 1C subunit.
1996,
Pubmed
,
Xenbase Zamponi,
Crosstalk between G proteins and protein kinase C mediated by the calcium channel alpha1 subunit.
1997,
Pubmed
,
Xenbase Zhang,
Multiple structural elements in voltage-dependent Ca2+ channels support their inhibition by G proteins.
1996,
Pubmed
,
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