Skip to main content
main-content
Erschienen in: Brain Structure and Function 1/2018

03.08.2017 | Original Article

Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain

verfasst von: Katherine E. Squires, Kyle J. Gerber, Jean-Francois Pare, Mary Rose Branch, Yoland Smith, John R. Hepler

Erschienen in: Brain Structure and Function | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein primarily expressed in mouse pyramidal neurons of hippocampal area CA2 where it regulates synaptic plasticity important for learning and memory. However, very little is known about RGS14 protein expression in the primate brain. Here, we validate the specificity of a new polyclonal RGS14 antibody that recognizes not only full-length RGS14 protein in primate, but also lower molecular weight forms of RGS14 protein matching previously predicted human splice variants. These putative RGS14 variants along with full-length RGS14 are expressed in the primate striatum. By contrast, only full-length RGS14 is expressed in hippocampus, and shorter variants are completely absent in rodent brain. We report that RGS14 protein immunoreactivity is found both pre- and postsynaptically in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra, and amygdala in adult rhesus monkeys. A similar cellular expression pattern of RGS14 in the monkey striatum and hippocampus was further confirmed in humans. Our electron microscopy data show for the first time that RGS14 immunostaining localizes within nuclei of striatal neurons in monkeys. Taken together, these findings suggest new pre- and postsynaptic regulatory functions of RGS14 and RGS14 variants, specific to the primate brain, and provide evidence for unconventional roles of RGS14 in the nuclei of striatal neurons potentially important for human neurophysiology and disease.
Literatur
Zurück zum Zitat Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375 CrossRefPubMed Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375 CrossRefPubMed
Zurück zum Zitat Ding J et al (2006) RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. Nat Neurosci 9:832–842. doi: 10.​1038/​nn1700 CrossRefPubMed Ding J et al (2006) RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. Nat Neurosci 9:832–842. doi: 10.​1038/​nn1700 CrossRefPubMed
Zurück zum Zitat Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432 CrossRefPubMed Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432 CrossRefPubMed
Zurück zum Zitat Gold SJ, Ni YG, Dohlman HG, Nestler EJ (1997) Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain. J Neurosci 17:8024–8037 PubMed Gold SJ, Ni YG, Dohlman HG, Nestler EJ (1997) Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain. J Neurosci 17:8024–8037 PubMed
Zurück zum Zitat Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ (2001) Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res 88:113–123 CrossRefPubMed Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ (2001) Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res 88:113–123 CrossRefPubMed
Zurück zum Zitat Graveland GA, DiFiglia M (1985) The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum. Brain Res 327:307–311 CrossRefPubMed Graveland GA, DiFiglia M (1985) The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum. Brain Res 327:307–311 CrossRefPubMed
Zurück zum Zitat Haber SN, Nauta WJ (1983) Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience 9:245–260 CrossRefPubMed Haber SN, Nauta WJ (1983) Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience 9:245–260 CrossRefPubMed
Zurück zum Zitat Haussler U, Rinas K, Kilias A, Egert U, Haas CA (2016) Mossy fiber sprouting and pyramidal cell dispersion in the hippocampal CA2 region in a mouse model of temporal lobe epilepsy. Hippocampus 26:577–588. doi: 10.​1002/​hipo.​22543 CrossRefPubMed Haussler U, Rinas K, Kilias A, Egert U, Haas CA (2016) Mossy fiber sprouting and pyramidal cell dispersion in the hippocampal CA2 region in a mouse model of temporal lobe epilepsy. Hippocampus 26:577–588. doi: 10.​1002/​hipo.​22543 CrossRefPubMed
Zurück zum Zitat Hollinger S, Hepler JR (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 54:527–559 CrossRefPubMed Hollinger S, Hepler JR (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 54:527–559 CrossRefPubMed
Zurück zum Zitat Hollinger S, Taylor JB, Goldman EH, Hepler JR (2001) RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain. J Neurochem 79:941–949 CrossRefPubMed Hollinger S, Taylor JB, Goldman EH, Hepler JR (2001) RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain. J Neurochem 79:941–949 CrossRefPubMed
Zurück zum Zitat Ingi T, Aoki Y (2002) Expression of RGS2, RGS4 and RGS7 in the developing postnatal brain. Eur J Neurosci 15:929–936 CrossRefPubMed Ingi T, Aoki Y (2002) Expression of RGS2, RGS4 and RGS7 in the developing postnatal brain. Eur J Neurosci 15:929–936 CrossRefPubMed
Zurück zum Zitat Kimple RJ, De Vries L, Tronchere H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP (2001) RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor activity. J Biol Chem 276:29275–29281. doi: 10.​1074/​jbc.​M103208200 CrossRefPubMed Kimple RJ, De Vries L, Tronchere H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP (2001) RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor activity. J Biol Chem 276:29275–29281. doi: 10.​1074/​jbc.​M103208200 CrossRefPubMed
Zurück zum Zitat Kuwajima M, Dehoff MH, Furuichi T, Worley PF, Hall RA, Smith Y (2007) Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of MPTP treatment and constitutive Homer deletion. J Neurosci 27:6249–6260. doi: 10.​1523/​JNEUROSCI.​3819-06.​2007 CrossRefPubMed Kuwajima M, Dehoff MH, Furuichi T, Worley PF, Hall RA, Smith Y (2007) Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of MPTP treatment and constitutive Homer deletion. J Neurosci 27:6249–6260. doi: 10.​1523/​JNEUROSCI.​3819-06.​2007 CrossRefPubMed
Zurück zum Zitat Labouebe G et al (2007) RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci 10:1559–1568. doi: 10.​1038/​nn2006 CrossRefPubMed Labouebe G et al (2007) RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci 10:1559–1568. doi: 10.​1038/​nn2006 CrossRefPubMed
Zurück zum Zitat Lifschytz T, Broner EC, Zozulinsky P, Slonimsky A, Eitan R, Greenbaum L, Lerer B (2012) Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement. Int J Neuropsychopharmacol 15:1307–1318. doi: 10.​1017/​S146114571100145​3 CrossRefPubMed Lifschytz T, Broner EC, Zozulinsky P, Slonimsky A, Eitan R, Greenbaum L, Lerer B (2012) Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement. Int J Neuropsychopharmacol 15:1307–1318. doi: 10.​1017/​S146114571100145​3 CrossRefPubMed
Zurück zum Zitat Mascagni F, McDonald AJ (2003) Immunohistochemical characterization of cholecystokinin containing neurons in the rat basolateral amygdala. Brain Res 976:171–184 CrossRefPubMed Mascagni F, McDonald AJ (2003) Immunohistochemical characterization of cholecystokinin containing neurons in the rat basolateral amygdala. Brain Res 976:171–184 CrossRefPubMed
Zurück zum Zitat McDonald AJ, Mascagni F (2001) Colocalization of calcium-binding proteins and GABA in neurons of the rat basolateral amygdala. Neuroscience 105:681–693 CrossRefPubMed McDonald AJ, Mascagni F (2001) Colocalization of calcium-binding proteins and GABA in neurons of the rat basolateral amygdala. Neuroscience 105:681–693 CrossRefPubMed
Zurück zum Zitat Mitrano DA, Pare JF, Smith Y (2010) Ultrastructural relationships between cortical, thalamic, and amygdala glutamatergic inputs and group I metabotropic glutamate receptors in the rat accumbens. J Comp Neurol 518:1315–1329. doi: 10.​1002/​cne.​22277 PubMedPubMedCentral Mitrano DA, Pare JF, Smith Y (2010) Ultrastructural relationships between cortical, thalamic, and amygdala glutamatergic inputs and group I metabotropic glutamate receptors in the rat accumbens. J Comp Neurol 518:1315–1329. doi: 10.​1002/​cne.​22277 PubMedPubMedCentral
Zurück zum Zitat Rahman Z et al (1999) Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. J Neurosci 19:2016–2026 PubMed Rahman Z et al (1999) Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. J Neurosci 19:2016–2026 PubMed
Zurück zum Zitat Rahman Z et al (2003) RGS9 modulates dopamine signaling in the basal ganglia. Neuron 38:941–952 CrossRefPubMed Rahman Z et al (2003) RGS9 modulates dopamine signaling in the basal ganglia. Neuron 38:941–952 CrossRefPubMed
Zurück zum Zitat Seeman P, Ko F, Jack E, Greenstein R, Dean B (2007) Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. Synapse 61:303–309. doi: 10.​1002/​syn.​20368 CrossRefPubMed Seeman P, Ko F, Jack E, Greenstein R, Dean B (2007) Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. Synapse 61:303–309. doi: 10.​1002/​syn.​20368 CrossRefPubMed
Zurück zum Zitat Shink E, Smith Y (1995) Differential synaptic innervation of neurons in the internal and external segments of the globus pallidus by the GABA- and glutamate-containing terminals in the squirrel monkey. J Comp Neurol 358:119–141. doi: 10.​1002/​cne.​903580108 CrossRefPubMed Shink E, Smith Y (1995) Differential synaptic innervation of neurons in the internal and external segments of the globus pallidus by the GABA- and glutamate-containing terminals in the squirrel monkey. J Comp Neurol 358:119–141. doi: 10.​1002/​cne.​903580108 CrossRefPubMed
Zurück zum Zitat Smith Y, Bevan MD, Shink E, Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86:353–387 CrossRefPubMed Smith Y, Bevan MD, Shink E, Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86:353–387 CrossRefPubMed
Zurück zum Zitat Vankova M, Arluison M, Leviel V, Tramu G (1992) Afferent connections of the rat substantia nigra pars lateralis with special reference to peptide-containing neurons of the amygdalo-nigral pathway. J Chem Neuroanat 5:39–50 CrossRefPubMed Vankova M, Arluison M, Leviel V, Tramu G (1992) Afferent connections of the rat substantia nigra pars lateralis with special reference to peptide-containing neurons of the amygdalo-nigral pathway. J Chem Neuroanat 5:39–50 CrossRefPubMed
Zurück zum Zitat Vellano CP, Brown NE, Blumer JB, Hepler JR (2013) Assembly and function of the regulator of G protein signaling 14 (RGS14).H-Ras signaling complex in live cells are regulated by Galphai1 and Galphai-linked G protein-coupled receptors. J Biol Chem 288:3620–3631. doi: 10.​1074/​jbc.​M112.​440057 CrossRefPubMed Vellano CP, Brown NE, Blumer JB, Hepler JR (2013) Assembly and function of the regulator of G protein signaling 14 (RGS14).H-Ras signaling complex in live cells are regulated by Galphai1 and Galphai-linked G protein-coupled receptors. J Biol Chem 288:3620–3631. doi: 10.​1074/​jbc.​M112.​440057 CrossRefPubMed
Zurück zum Zitat Wilson CJ, Groves PM (1980) Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: a study employing intracellular inject of horseradish peroxidase. J Comp Neurol 194:599–615. doi: 10.​1002/​cne.​901940308 CrossRefPubMed Wilson CJ, Groves PM (1980) Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: a study employing intracellular inject of horseradish peroxidase. J Comp Neurol 194:599–615. doi: 10.​1002/​cne.​901940308 CrossRefPubMed
Zurück zum Zitat Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R (2002) Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110:443–455 CrossRefPubMed Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R (2002) Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110:443–455 CrossRefPubMed
Metadaten
Titel
Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain
verfasst von
Katherine E. Squires
Kyle J. Gerber
Jean-Francois Pare
Mary Rose Branch
Yoland Smith
John R. Hepler
Publikationsdatum
03.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 1/2018
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-017-1487-y

Weitere Artikel der Ausgabe 1/2018

Brain Structure and Function 1/2018 Zur Ausgabe

Neu im Fachgebiet Neurologie

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Neurologie und bleiben Sie gut informiert – ganz bequem per eMail.