GABAB receptors function as heterodimers

Marshall, Fiona H.; White, J. L.; Main, Martin J.; Green, Andrew; Wise, Alan

doi:10.1042/bst0270530

Cited by 47 publications

(26 citation statements)

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“…In 1987 homodimerization was found to take place upon epidermal growth factor (EGF) induced stimulation of the epidermal growth hormone receptor [11]. Ten years later the demonstration of the GABA B receptor heterodimer (see [12][13][14]) validated our early findings indicating receptor-receptor interactions in putative GPCR heteroreceptor complexes [2,8]. Thus, the entire decoding process becomes a branched process already at the receptor level in the plasma membrane.…”

Section: Introductionsupporting

confidence: 59%

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Receptor-receptor interactions in heteroreceptor complexes: a new principle in biology. Focus on their role in learning and memory

Fuxé

Borroto‐Escuela²,

Ciruela³

et al. 2014

Neurosci Discov

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The allosteric receptor-receptor interactions over the interfaces in heteroreceptor complexes have been explored and their biochemical, pharmacological and functional integrative implications in the Central Nervous System (CNS) described. GPCR interacting proteins participate in these complexes mainly through modulation of receptor-receptor interactions. Methodologies to study heteroreceptor complexes in living cells (FRET and BRET-based techniques) and in brain tissue (in situ proximity ligation assay) are briefly summarized. The physiological and pathological relevance of the allosteric receptor-receptor interactions in heteroreceptor complexes is emphasized and novel strategies for treatment of mental and neurological disease are developed based on this new biological principle of integration. The molecular basis of learning and memory is proposed to be based on the reorganization of the homo-and heteroreceptor complexes in the postjunctional membrane of synapses leading also to changes in the prejunctional receptor complexes to facilitate the pattern of transmitter release to be learned. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins which can consolidate the heteroreceptor complexes into long-lived complexes with conserved allosteric receptor-receptor interactions.

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Section: Introductionsupporting

confidence: 59%

“…The receptor-receptor interaction may also make possible the appearance of novel receptor subtypes like the GABA B receptor [12,13]. Furthermore, the A 1 R-P 2 Y 1 R heteroreceptor complexes show an A 1 R with P 2 Y 1 R agonist like recognition [106].…”

Section: Physiological and Pathological Relevance Of The Allosteric Rmentioning

confidence: 99%

Receptor-receptor interactions in heteroreceptor complexes: a new principle in biology. Focus on their role in learning and memory

Fuxé

Borroto‐Escuela²,

Ciruela³

et al. 2014

Neurosci Discov

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“…The concept of GPCR oligomerization was later confirmed in 1998-1999 by studies reporting that two nonfunctional class C GPCR monomers, GABA B1 and GABA B2 , assembled in a signaling heterodimer (Marshall et al, 1999a). In the years that followed, several groups provided direct evidence for the existence of receptor complexes formed by GPCR (Fuxe et al, 1998;Bockaert and Pin, 1999;Marshall et al, 1999b;Xie et al, 1999;Franco et al, 2000;Lee et al, 2000;Overton and Blumer, 2000;Zeng and Wess, 2000;Angers et al, 2001;Dean et al, 2001;Kenakin, 2002;Waldhoer et al, 2005).…”

Section: Introductionmentioning

confidence: 77%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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Abstract:The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.

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“…Fully functional GABA B receptors require the coassembly of the two different subunits, since neither the GABA B1 nor the GABA B2 is active when expressed independently (194,294,311,361,524,662). However, when coexpressed, recombinant GABA B1,2 receptors mediate all predominant effects of native receptors, i.e., modulation of cAMP production, activation of GIRK channels, and inhibition of P/Q-and N-type Ca 2ϩ channels (175,194,416). Moreover, in GABA B1 or GABA B2 knockout mice, all GABA B receptor-mediated functions were absent (226,511,547).…”

Section: B Gaba B Receptorsmentioning

confidence: 99%

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

Ben-Ari

Gaı̈arsa

Tyzio

et al. 2007

Physiological Reviews

1,137

1,123

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Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter γ-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABAAreceptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to “wire together” so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

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GABAB receptors function as heterodimers

Cited by 47 publications

References 1 publication

Receptor-receptor interactions in heteroreceptor complexes: a new principle in biology. Focus on their role in learning and memory

Receptor-receptor interactions in heteroreceptor complexes: a new principle in biology. Focus on their role in learning and memory

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

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