Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes

Borroto-Escuela, Dasiel O.; Romero-Fernández, Wilber; Narváez, Manuel; Oflijan, Julia; Agnati, Luigi F.

doi:10.1016/j.bbrc.2013.11.104

Cited by 84 publications

(70 citation statements)

References 21 publications

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“…Taken together, the findings indicate that in situ PLA can be used to demonstrate heteroreceptor complexes ex vivo in doi: 10.7243/2052-6946-2-6 brain tissue like the striatal A 2A R-D 2 R heteroreceptor complexes [39,40] and the accumbal and dorsal striatal D 2 R-5HT 2A R heteroreceptor complexes [42].…”

Section: Review Methodologies For Studies On Protein-protein Interactmentioning

confidence: 96%

“…This sequential reaction process (antibody recognition, joining of oligonucleotides, ligation, amplification and hybridization) rendered the heteroreceptor complexes observable by fluorescence microscopy. In this way you can study the number, localization and modulation of CNS heteroreceptor complexes since formalin fixed tissue is used [21,[39][40][41][42][43][44][45]. The main drawback of in situ PLA lies in the quality of fixed tissue, the specificity and bivalent character of the primary antibodies and the use of proper controls.…”

Section: Review Methodologies For Studies On Protein-protein Interactmentioning

confidence: 99%

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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: Review Methodologies For Studies On Protein-protein Interactmentioning

confidence: 96%

Section: Review Methodologies For Studies On Protein-protein Interactmentioning

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

Self Cite

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show abstract

“…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%

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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113

130

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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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“…This relationship has been demonstrated in animal paradigms at the postsynaptic density level and in intracellular machinery (for review, see de Bartolomeis et al, 2013). It has been reported that these receptors are expressed as a functional heterooligomer in discrete regions of the ventral and dorsal striata and in HEK293 cells after co-transfection of both receptors (BorrotoEscuela et al, 2010;Lukasiewicz et al, 2010;Albizu et al, 2011;Borroto-Escuela et al, 2014). The heterocomplex formation is involved in conditioning the response of both receptors to hallucinogenic ligands and antipsychotic drugs.…”

Section: Introductionmentioning

confidence: 90%

“…We found 100 lM (±) DOI induced an increase of The distribution of these heteromers is compatible with dendritic localization (Borroto-Escuela et al, 2014). Based on the 50% decrease in reelin expression observed in schizophrenic patients and a decrease in dendritic spines, we aimed to ascertain how the reelin decrease could also affect the expression and function of D 2 and 5-HT 2A receptors.…”

Section: Functional Activity Of 5-ht 2a Serotonin Receptors In Mouse mentioning

confidence: 98%

Reelin influences the expression and function of dopamine D2 and serotonin 5-HT2A receptors: A comparative study

et al. 2015

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Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes

Cited by 84 publications

References 21 publications

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

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

Reelin influences the expression and function of dopamine D2 and serotonin 5-HT2A receptors: A comparative study

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