Subcellular vesicular aggregations of GABAB R1a and R1b receptors increase with age in neurons of the developing mouse brain

Ritter, Barbara; Ochojski, M.; Kuhn, Terra M.; Schwarzacher, Stephan W.; Zhang, W.

doi:10.1007/s00441-004-0991-6

Cited by 7 publications

(3 citation statements)

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“…Further heterogeneity could be predicted from putative interactions involving the extracellular "sushi domains" (59) or formation of intracellular complexes between GABA A R-␥2S and GABA B R1 (60) or RGS-mediated binding to coupled GIRK channels (61). The striking "vesicular" appearance of the GABA B R staining pattern, previously described in neurons (62) and Schwann cells (27), is consistent with the existence of multiprotein GABA B R2-containing complexes.…”

Section: Discussion Mesc and Gabar Expressionsupporting

confidence: 58%

GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺

et al. 2009

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Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca(2+))-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca(2+) transients involving both VGCC-mediated Ca(2+) influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca(2+) transients followed by intercellular Ca(2+) waves and oscillations that were resistant to antagonists and entirely dependent on Ca(2+) release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Máté, Z., Katarova, Z., Szabó, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+).

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Section: Discussion Mesc and Gabar Expressionsupporting

confidence: 58%

GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺

et al. 2009

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“…GABA-B 1 receptor subunits, which remain in the endoplasmic reticulum (ER) in the absence of GABA-B 2 subunits (102–105). However, the distribution of GABA-B 1 in the central nervous system is much broader than that of GABA-B 2 , which suggests that this receptor may have an independent function intracellularly (106–108). It was demonstrated that a recently deorphanized GPCR, GPR30, targeted exclusively to the ER, is a functional receptor for estrogen (109).…”

Section: Gβγ Subunits and Effectors Localized At Sites Distinct From mentioning

confidence: 99%

The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes

Dupré

Robitaille

Rebois

et al. 2009

Annu. Rev. Pharmacol. Toxicol.

234

194

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The role of Gβγ subunits in cellular signaling has become well established in the past 20 years. Not only do they regulate effectors once thought to be the sole targets of Gα subunits, but it has become clear that they also have a unique set of binding partners and regulate signaling pathways that are not always localized to the plasma membrane. However, this may be only the beginning of the story. Gβγ subunits interact with G protein-coupled receptors, Gα subunits, and several different effector molecules during assembly and trafficking of receptor-based signaling complexes and not simply in response to ligand stimulation at sites of receptor cellular activity. Gβγ assembly itself seems to be tightly regulated via the action of molecular chaperones and in turn may serve a similar role in the assembly of specific signaling complexes. We propose that specific Gβγ subunits have a broader role in controlling the architecture, assembly, and activity of cellular signaling pathways.

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“…Funcional GABA B receptors are present in pre-Bötzinger complex of neonatal mice GABA B receptors have been shown to be expressed (Lopez-Bendito et al, 2002;Ritter et al, 2005) and functional (Zhang et al, 2002) at early stages of development.…”

Section: 1mentioning

confidence: 99%

Funktion und die Signalübertragung der GABAB-Rezeptoren im respiratorischem Netzwerk der Maus

Sargsyan¹

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Amino-5-phosphonovaleric acid EDTA Ethylenedinitrilo-tetraacetic acid et al. et alters (and others) g Gravitational acceleration, or gram GABA γ-aminobutyric acid GΩ Giga Ohm HEPES 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid KO Knockout µ-micro,-( x 10 -6 ) mV millivolts m. minute NA Nucleus ambiguus NGS Normal goat serum NH Nucleus hypoglossus NMDA N-methyl-D-Aspartate N-terminal at the NH2-terminus of a protein pA pico Ampere PBC PreBötzinger complex PBS Phosphate buffer saline PFA paraformaldehyde pH Negative logarithm of H + -concentration PDZ Protein interaction domain, acronym for PSD-95, Dlg, ZO-1 PSD postsynaptic density RT Room temperature s. second SDS Sodium dodecyl sulfate sIPSC spontaneous postsynaptic currents sPSC spontaneous postsynaptic currents Tris Tris-hydroxymethyl-aminomethane WT Wild type 5′ 5 prime 3′ 3 prime Contents 1. Contents 3.5.5 Involvement of G βγ subunits of G-proteins in GABA B mediated modulation of I h current 4. Discussion 4.1 Functional GABA B receptors are present in pre-Bötzinger complex of neonatal mice 4.2 The essential role of GABA B receptors in a network sensing extracellular pH 4.3 Identification and developmental changes of I h current in pre-Bötzinger complex 4.4 GABA B modulates I h currents 4.5 The mechanism of I h modulation by GABA B 4.6 Concluding remarks and future outlook 5. Summary 6. Acknowledgements 7. References 8. Curriculum Vitae 9. Publication list 1.1998). This, in turn leads to fusion of neurotransmitter containing vesicles with the plasma membrane and the release of the content into synaptic cleft, thereby activating receptors on the postsynaptic membrane. The synapses can be inhibitory and excitatory. The excitation is mediated mainly by glutamate receptors, while inhibition is mediated by GABA and glycine receptors. GABA-ergic neurotransmissionγ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain. There are two distinct categories of target receptors for GABA, each of which mediates synaptic transmission: ionotropic GABA A and GABA C , and metabotropic GABA B receptors. GABA A receptors are ligand-gated Cl − -channels that mediate fast localization of GABA B1a (Benke et al., 1999;Princivalle et al., 2001). During postnatal development there is up-and downregulation of both isoforms (Fritschy et al., 2004).GABA B1a has been found to be predominantly expressed in neonatal mice with overlapping regional distribution with GABA B2 , but with profound distinctions in cellular and subcellular localizations. GABA B1b is expressed in adult mice, together with GABA B2 . Studies monitoring functional GABA B responses suggest their presence in Many mechanisms that include changes in intracellular levels of cAMP do, therefore, modulate I h channels due to unique property of these channels to be directly gated by cAMP (Tokimasa and Akasu, 1990). Thus, neurotransmitters that alter the basal activity of adenylyl cyclases, have been shown to modulate I h (

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Subcellular vesicular aggregations of GABAB R1a and R1b receptors increase with age in neurons of the developing mouse brain

Cited by 7 publications

References 34 publications

GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺

GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺

The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes

Funktion und die Signalübertragung der GABAB-Rezeptoren im respiratorischem Netzwerk der Maus

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Subcellular vesicular aggregations of GABAB R1a and R1b receptors increase with age in neurons of the developing mouse brain

Cited by 7 publications

References 34 publications

GABAAand GABABreceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+

GABAAand GABABreceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+

The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes

Funktion und die Signalübertragung der GABAB-Rezeptoren im respiratorischem Netzwerk der Maus

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GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺

GABA_Aand GABA_Breceptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca²⁺