Existence of muscarinic acetylcholine receptor (mAChR) and fibroblast growth factor receptor (FGFR) heteroreceptor complexes and their enhancement of neurite outgrowth in neural hippocampal cultures

Liberto, Valentina Di; Borroto-Escuela, Dasiel O.; Frinchi, Monica; Verdi, Vincenzo; Fuxé, Kjell; Belluardo, Natale; Mudò, Giuseppa

doi:10.1016/j.bbagen.2016.10.026

Cited by 41 publications

(51 citation statements)

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“…Although a specific investigation is needed to identify the type of mAChR involved, by literature data and our experience we can hypothesize some possibilities involving M 1 R or M 3 R receptors. Previously, we showed that M 1 R are involved in FGFR1 transactivation in Oxo treatment‐induced neuronal axonal growth (Di Liberto, Borroto‐Escuela, et al, ). Recently, it has been shown that M 3 R activation leads to enhancement of Hsp70 and Hsp90 expression and phosphorylation of HSF1 (Mahati et al, ).…”

Section: Discussionmentioning

confidence: 93%

“…Additionally, in order to unveil a temporal behavior of the Oxo effect within each type of treatment, we analyzed a time-course with three time points: 24, 48, and 72 hr from treatment, with exclusion of 10 days treatment in which we analyzed the time points 24 and 72 hr from treatment. For the single injection, we chose the Oxo dose of 0.4 mg/kg and for chronic treatment the dose of 0.2 mg/kg in relation to previous experience (Di Liberto, Frinchi, et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…Alzheimer's disease (Hoshino et al, 2011), and neuroplasticity (Di Liberto et al, 2014;Di Liberto, Borroto-Escuela, et al, 2017;Di Liberto, Frinchi, et al, 2017).…”

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confidence: 99%

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Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Frinchi

Scaduto

Cappello

et al. 2018

Journal Cellular Physiology

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The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1). Following single injection of Oxotremorine-M (0.4 mg/kg) all Hsps examined were significantly increased in at least one of the time points studied (24, 48, and 72 hr). Treatment with Oxotremorine-M significantly increased the level of phosphorylated HSF1 in all time points studied, without change of protein levels. Similar pattern of Hsps changes was obtained following chronic Oxotremorine-M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic treatment for 10 days no changes were observed in Hsps. The muscarinic acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely block Oxotremorine-M effects on Hsps. In conclusion, considering the function of Hsps in protecting neuronal cells from deleterious proteotoxic stress, for example, protein mis-folding and aggregation, the results obtained indicate that muscarinic acetylcholine receptor activation may have implications in potential treatment of neurodegenerative disorders linked to protein aggregation, such as Alzheimer disease.

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Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Frinchi

Scaduto

Cappello

et al. 2018

Journal Cellular Physiology

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“…Recently identified direct interactions with RTK (BorrotoEscuela et al, 2012;Di Liberto et al, 2017), indeed, open the possibility that GPCR complexes could modulate structural changes at the level of dendrites and dendritic spines. Furthermore, the reorganization of GPCR complexes in the postjunctional membrane of synapses and their possible stabilization by the interaction with specific adapter proteins could represent a molecular mechanism for learning and memory Fuxe et al, 2014b;Borroto-Escuela et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Processes of transactivation of RTK by GPCR have been reported (Flajolet et al, 2008;Asimaki et al, 2011;Di Liberto et al, 2014), generating neuroplasticity in cultured neurons. Recently, however, the formation (by direct RRI) of receptor complexes involving fibroblast growth factor receptor 1 and 5-HT 1A or muscarinic M 1 receptor (Di Liberto et al, 2017) have been identified in the hippocampus with increased neurite densities after agonist coactivation.…”

Section: Rm and Hmnsmentioning

confidence: 99%

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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2023

Concepts in Biology

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Existence of muscarinic acetylcholine receptor (mAChR) and fibroblast growth factor receptor (FGFR) heteroreceptor complexes and their enhancement of neurite outgrowth in neural hippocampal cultures

Cited by 41 publications

References 64 publications

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

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

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