Receptor-Receptor Interactions in the Central Nervous System

doi:10.1007/978-1-4939-8576-0

Cited by 15 publications

(2 citation statements)

References 12 publications

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“…In view of the above, it seems possible that integration in the T-cells not only involves changes in the signaling of the inhibitory and facilitatory immunoreceptors and integration of their intracellular pathways, but also their integration in immune synapses with the antigen presenting cells including the tumor cells. Based on the work in the CNS [see book edited by Fuxe and Borroto-Escuela (14)] it seems likely that integration in the immune system also involves the dynamic formation and operation of homo-and heteroreceptor complexes (Figure 1). The T cell receptor and the T cell accelerator receptors enhancing the immune response may form heteroreceptor complexes with the immunoinhibitory receptors CTLA4 and PD-1 inhibiting the immune responses in which the major integration of immune and transmitter/modulator signals take place (Figure 1).…”

Section: Understanding the Mechanisms Of Cancer Therapy Based On Protmentioning

confidence: 99%

“…Many of the homo and heteroreceptor complexes studied so far are mainly found in the extrasynaptic and synaptic regions of the plasma membrane of the neuronal networks using in situ Proximity Ligation Assay (PLA) and a neuronal marker antibody (14, 50). However, they can also exist in e.g., the astroglia based on PLA and astroglial markers like antibodies against glial fibrillary acidic protein.…”

Section: Integration Of Signaling In the Cns Support The Above Hypothmentioning

confidence: 99%

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Can Allosteric Receptor-Protein Interactions in Receptor Complexes Be a Molecular Mechanism Involved in Cancer Immune Therapy?

Borroto-Escuela

Fuxé

2019

Front. Endocrinol.

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Based on the work in the Central Nervous System with discoveries of allosteric receptor-receptor interactions in homo- and heteroreceptor complexes representing a major integrative mechanism in synapses and extrasynaptic regions, it is proposed that a similar mechanism may exist in the immunological synapses. We discuss a putative additional molecular mechanism for the ability of the inhibitory T cell signaling proteins CTLA-4 and PD-1 and the adenosine A2AR to diminish T cell activation leading to enhancement of cancer development. We suggest that in the same immunological synapse involving T cells and antigen presenting cells multiple heteroreceptor complexes may participate and be in balance with each other. Their composition can vary between functional states and among different types of T cells. The T cell receptor (TCR) and its accelerators, strongly enhancing T cell activation, can be under inhibitory control by T cell signaling proteins CTLA4 and PD-1 and also the adenosine A2AR through inhibitory allosteric receptor-receptor interactions in different types of heteroreceptor complexes. As a result, inhibitory tumor induced immunosuppression can develop due to a dominance of the inhibitory signaling causing a brake on the TCR and/or its accelerator and the cancer immunotherapy becomes blocked.

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Section: Understanding the Mechanisms Of Cancer Therapy Based On Protmentioning

confidence: 99%

Section: Integration Of Signaling In the Cns Support The Above Hypothmentioning

confidence: 99%

Can Allosteric Receptor-Protein Interactions in Receptor Complexes Be a Molecular Mechanism Involved in Cancer Immune Therapy?

Borroto-Escuela

Fuxé

2019

Front. Endocrinol.

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Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

Borroto-Escuela

Pita-Rodríguez

Fores-Pons

et al. 2020

Journal Cellular Physiology

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A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5‐Bromo‐2'‐deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG). We employed in situ proximity ligation assay to manifest GALR2/NPYY1R heteroreceptor complexes. Additionally, the expression pattern of GALR2 and the activation of the extracellular‐regulated kinases (ERK) pathway after GALR2 and NPYY1R costimulation in cell cultures were examined. GALR2 and NPYY1R coactivation resulted in sustained antidepressant behaviors in the FST after 24 h, linked to increased cell proliferation in the vDG. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was observed in vDG, on doublecortin‐expressing neuroblasts. Recruitment of the GALR2 expression to the plasma membrane was observed upon the coactivation of GALR2 and NPYY1R in cell cultures, presumably associated to the enhanced effects on the activation of ERK pathway. GALR2 may promote the GALR2/NPYY1R heteroreceptor complexes formation in the ventral hippocampus. It may induce a transformation of cell proliferation toward a neuronal lineage by enhancement of ERK pathway. Thus, it may give the mechanism for the antidepressant behavior observed. These results may provide the basis for the development of heterobivalent agonist pharmacophores, targeting GALR2/NPYY1R heteromers, especially in the neuronal precursor cells of the dentate gyrus in the ventral hippocampus for the novel treatment of depression.

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Study of GPCR Homo- and Heteroreceptor Complexes in Specific Neuronal Cell Populations Using the In Situ Proximity Ligation Assay

et al. 2021

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Receptor-Receptor Interactions in the Central Nervous System

Cited by 15 publications

References 12 publications

Can Allosteric Receptor-Protein Interactions in Receptor Complexes Be a Molecular Mechanism Involved in Cancer Immune Therapy?

Can Allosteric Receptor-Protein Interactions in Receptor Complexes Be a Molecular Mechanism Involved in Cancer Immune Therapy?

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

Study of GPCR Homo- and Heteroreceptor Complexes in Specific Neuronal Cell Populations Using the In Situ Proximity Ligation Assay

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