Fibroblast Growth Factor Receptor 1– 5-Hydroxytryptamine 1A Heteroreceptor Complexes and Their Enhancement of Hippocampal Plasticity

Borroto-Escuela, Dasiel O.; Romero-Fernández, Wilber; Mudò, Giuseppa; Pérez-Alea, Mileidys; Ciruela, Francisco; Tarakanov, Alexander O.; Narváez, Manuel; Liberto, Valentina Di; Agnati, Luigi F.; Belluardo, Natale; Fuxé, Kjell

doi:10.1016/j.biopsych.2011.09.012

Cited by 117 publications

(149 citation statements)

References 27 publications

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“…A protriplet TLG (Thr-Leu-Gly) amino acid homology was discovered in the intracellular domains of the two receptors which can participate in the mediation of the interaction. This homology was also found in the intracellular domains of an indicated FGFR1-5-HT1B heterodimer (table 1 and figure 2) [27] but was absent in two non-heteromers (FGFR1-5-HT2A, FGFR1-5-HT2C; table 1). The TLG homology was also present in a FGFR1-5-HT7 pair near the border between intracellular domain and TM6 (see ic3jTM6 in figure 2).…”

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 61%

“…CNS, since the stoichiometry is unknown and adaptor proteins and other types of proteins (e.g. ion channels, transporters) are known to participate through direct interactions with the receptors [24,25,27,[74][75][76].…”

Section: (B) On the Renewal And Clearance Of Volume Transmission Signmentioning

confidence: 99%

“…Thus, GPCR protomers can moonlight through the allosteric receptor-receptor interactions [83,84] through changes in recognition, G protein selectivity and signalling cascades with, among other things, switching from activating G proteins to beta-arrestin or calmodulin through conformational changes in single or several strands of amino acids of intracellular loops and the C-terminal tail [85,86]. It is hypothesized that GPCR protomer function may also change by becoming linked to receptor tyrosine kinase (RTK) signalling in GPCR-RTK heteroreceptor complexes and involved in trophic functions [22,27,[87][88][89][90][91], and through formation of GPCR-ion channel heteroreceptor complexes like NMDA-D1 and D2-NR2B complexes, a field pioneered by Fang Liu and colleagues [92][93][94]. GPCRs may become capable of modulating neuronal excitability and firing patterns in a novel way through changes in NMDA receptor function [92,[95][96][97].…”

Section: (B) On the Renewal And Clearance Of Volume Transmission Signmentioning

confidence: 99%

“…During recent years, a number of 5-HT1A heteroreceptor complexes have been identified [27,88,90,114], the first one discovered being the galanin receptor1(GalR1)-5-HT1A heteromer. They are hypothesized to represent novel targets for antidepressant drugs; previously, only 5-HT1A had been considered as a target.…”

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 99%

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The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

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110

119

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One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, the prototype being synaptic transmission with axons and terminals) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid (CSF)) involving large numbers of cells in the CNS. Volume and synaptic transmission become integrated inter alia through the ability of their chemical signals to activate different types of receptor protomers in heteroreceptor complexes located synaptically or extrasynaptically in the plasma membrane. The demonstration of extracellular dopamine (DA) and serotonin (5-HT) fluorescence around the DA and 5-HT nerve cell bodies with the Falck-Hillarp formaldehyde fluorescence method after treatment with amphetamine and chlorimipramine, respectively, gave the first indications of the existence of VT in the brain, at least at the soma level. There exist different forms of VT. Early studies on VT only involved spread including diffusion and flow of soluble biological signals, especially transmitters and modulators, a communication called extrasynaptic (short distance) and long distance (paraaxonal and paravascular and CSF pathways) VT. Also, the extracellular vesicle type of VT was demonstrated. The exosomes (endosome-derived vesicles) appear to be the major vesicular carriers for VT but the larger microvesicles also participate. Both mainly originate at the soma-dendritic level. They can transfer lipids and proteins, including receptors, Rab GTPases, tetraspanins, cholesterol, sphingolipids and ceramide. Within them there are also subsets of mRNAs and non-coding regulatory microRNAs. At the soma-dendritic membrane, sets of dynamic postsynaptic heteroreceptor complexes (built up of different types of physically interacting receptors and proteins) involving inter alia G protein-coupled receptors including autoreceptors, ion channel receptors and receptor tyrosine kinases are hypothesized to be the molecular basis for learning and memory. At nerve terminals, the presynaptic heteroreceptor complexes are postulated to undergo plastic changes to maintain the pattern of multiple transmitter release reflecting the firing pattern to be learned by the heteroreceptor complexes in the postsynaptic membrane.

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Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 61%

Section: (B) On the Renewal And Clearance Of Volume Transmission Signmentioning

confidence: 99%

Section: (B) On the Renewal And Clearance Of Volume Transmission Signmentioning

confidence: 99%

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 99%

See 2 more Smart Citations

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

Self Cite

110

119

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“…In addition, the methods were employed to demonstrate for the first time the existence of FGFR1 and 5-HT1A receptor heterocomplexes in the rat hippocampus and dorsal and median raphe in the midbrain ( Fig. 15.3A; Borroto-Escuela et al, 2012).…”

Section: P0155mentioning

confidence: 99%

G Protein–Coupled Receptor Heterodimerization in the Brain

Borroto-Escuela

Romero-Fernández

Garriga

et al. 2013

Methods in Enzymology

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111

103

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Drug‐resistant epilepsy: Drug target hypothesis and beyond the receptors

Fonseca-Barriendos¹,

Frías‐Soria²,

Pérez-Pérez³

et al. 2021

Epilepsia Open

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Epilepsy is a common chronic neurological disorder that affects more than 50 million people worldwide. 1 Antiseizure drug that serves as the first line of treatment is used to control seizures. However, one-third of patients with epilepsy suffer from drug-resistant epilepsy (DRE) because they fail to achieve control of seizures despite the appropriate treatment schemes used (in monotherapy or various combinations). 2 According to the target hypothesis that explains the drug-resistance phenotype in epilepsy, failure to control epileptic activity by antiseizure medication (ASM) results in losing therapeutic efficacy as a consequence of alterations in the structure and/or function of their targets 3 (Figure 1). In this regard, adopting different therapeutic targets in patients with DRE is crucial, which include alterations in voltage-gated sodium channels (VGSCs) and γ-aminobutyric acid (GABA) receptors.Some studies confirm that resected brain tissue obtained from patients with drug-resistant temporal lobe epilepsy (DR-TLE) who have undergone surgery show reduced sensitivity to carbamazepine, a drug that inhibits VGSC. 4,5 Experimental models have not yet reproduced this condition in DRE. However, studies in models of acute seizures and epilepsy have demonstrated induced alterations in VGSC similar to those detected in brain tissue of patients with the DRE. [6][7][8]

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Fibroblast Growth Factor Receptor 1– 5-Hydroxytryptamine 1A Heteroreceptor Complexes and Their Enhancement of Hippocampal Plasticity

Cited by 117 publications

References 27 publications

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

G Protein–Coupled Receptor Heterodimerization in the Brain

Drug‐resistant epilepsy: Drug target hypothesis and beyond the receptors

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