Sequential onset of three 5‐HT receptors during the 5‐hydroxytryptaminergic differentiation of the murine 1C11 cell line

Kellermann, Odile; Loric, Sylvain; Maroteaux, Luc; Launay, Jean‐Marie

doi:10.1111/j.1476-5381.1996.tb15519.x

Cited by 31 publications

(44 citation statements)

References 34 publications

(47 reference statements)

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“…These levels might thus reflect a constitutive basal activity of the 5-HT 2B receptor. Such a basal activity has already been observed for its PLC␤ (4,23), ras-mitogenactivated protein kinase (8), and phospholipase A 2 (5) couplings.…”

Section: -Ht 2b Receptors Are Coupled To Both Cnos and Inos Activitisupporting

confidence: 57%

“…Radioligand Binding Experiments-Radioligand binding experiments were performed as previously detailed (4,23 twice in fresh serum-free medium and incubated for various times at 37°C with l00 M isobutylmethylxanthine and test agents. The reaction was stopped by aspiration of the medium followed by addition of 500 l ice-cold 95% ethanol/5% formic acid (1:1, v/v).…”

Section: Methodsmentioning

confidence: 99%

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PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

Manivet

Mouillet-Richard

Crinon

et al. 2000

Journal of Biological Chemistry

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115

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Taking advantage of three cellular systems, we established that 5-HT 2B receptors are coupled with NO signaling pathways. In the 1C11 serotonergic cell line and Mastomys natalensis carcinoid cells, which naturally express the 5-HT 2B receptor, as well as in transfected LMTK ؊ fibroblasts, stimulation of the 5-HT 2B receptor triggers intracellular cGMP production through dual activation of constitutive nitric-oxide synthase (cNOS) and inducible NOS (iNOS). The group I PDZ motif at the C terminus of the 5-HT 2B receptor is required for recruitment of the cNOS and iNOS transduction pathways. Indeed, the 5-HT 2B receptor-mediated NO coupling is abolished not only upon introduction of a competitor C-terminal 5-HT 2B peptide in the three cell types but also in LMTK ؊ fibroblasts expressing a receptor C-terminally truncated or harboring a point mutation within the PDZ domain. The occurrence of a direct functional coupling between the receptor and cNOS activity is supported by highly significant correlations between the binding constants of drugs on the receptor and their effects on cNOS activity. The 5-HT 2B /iNOS coupling mechanisms appear more complex because neutralization of endogenous G␣ 13 by specific antibodies cancels the cellular iNOS response while not interfering with cNOS activities. These findings may shed light on physiological links between the 5-HT 2B receptor and NO and constitute the first demonstration that PDZ interactions participate in downstream transductional pathways of a G protein-coupled receptor.The monoamine serotonin (5-hydroxytryptamine; 5-HT) 1 modulates a wide variety of human behavioral and physiological processes, such as sleep, anxiety, and cognition, as well as memory, perception, cardiovascular function, smooth muscle response, and gastrointestinal contraction (1, 2). So far, the diversity of 5-HT receptors and the lack of specific pharmacological tools have impaired the investigation of the precise roles of these proteins in the signaling networks that mediate 5-HT physiological functions. This is particularly true in the case of the 5-HT 2B receptor, which, like all the 15 known mammalian 5-HT receptor subtypes but one (5-HT 3 ), belongs to the G protein-coupled receptors (GPCRs). 5-HT 2B receptors cDNA were cloned from the rat stomach fundus, mouse brain, human liver, and neuroblastoma cell lines (see Ref. 3 for review). The 5-HT 2B receptor could be expressed either by transfection or endogeneously during the serotonergic neuronal differentiation of 1C11 cells, referred to as 1C11* /5HT cells (4, 5). In both cases, the receptor couples with PIP 2 hydrolysis, similarly to the two other members (5-HT 2A and 5-HT 2C ) of the 5-HT 2 receptor family. In contrast, the 5-HT 2B receptor stimulation fails to stimulate PIP 2 hydrolysis in rat fundus (6) and in rat vasculature (7). Signaling processes involving 5-HT 2B receptors and distinct from PIP 2 hydrolysis might thus occur. Accordingly, 5-HT 2B -dependent activations of both the ras-mitogen-activated protein kinase cascade (8) and ...

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Section: -Ht 2b Receptors Are Coupled To Both Cnos and Inos Activitisupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

Manivet

Mouillet-Richard

Crinon

et al. 2000

Journal of Biological Chemistry

Self Cite

115

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“…5-HT cells at day 2 of serotonergic differentiation when 5-HT 2A receptors are not yet present (9,18). As already mentioned in Fig.…”

Section: Prpmentioning

confidence: 69%

“…Radioligand Binding Experiments-Radioligand binding experiments were as described previously (17,18). Experiments were performed using 1C11 5-HT cells or mouse LMTK Ϫ fibroblasts stably transfected with cDNA encoding the mouse 5-HT 2A or 5-HT 2B receptor.…”

mentioning

confidence: 99%

Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein*

Mouillet-Richard

Pietri

Schneider

et al. 2005

Journal of Biological Chemistry

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C -caveolin platform implemented on the neurites of 1C115-HT cells during differentiation. Our findings define PrP C as a modulator of 5-HT receptor coupling to G-proteins and thereby as a protagonist contributing to the homeostasis of serotonergic neurons. They provide a foundation for uncovering the impact of prion infection on serotonergic functions.Some aspects of serotonin (5-hydroxytryptamine (5-HT) 1 ) homeostasis may relate to the plasticity of serotonergic neurons, which continually adapt their phenotype in response to 5-HT as well as to a variety of neuronal and non-neuronal factors (1). In addition to releasing 5-HT, serotonergic neurons of the raphe nuclei contribute to the integration of 5-HT signals by expressing 5-HT receptors, including 5-HT 1A , 5-HT 1B/D , 5-HT 2A , and 5-HT 2B subtypes (2). These receptors most likely behave as autoreceptors modulating 5-HT-related cellular functions (3, 4). However it is unclear whether the same neurons or distinct subpopulations harbor these receptor subtypes. The complexity of serotonergic signaling networks is far from being solved. Indeed, the targets recruited by 5-HT receptor-mediated signals are poorly characterized. Besides, still little is known about cross-talks between signaling cascades coupled with a single 5-HT receptor subtype and/or between pathways related to distinct receptor subclasses.Taking advantage of the 1C11 murine neuroectodermal cell line, which is endowed with the capacity to undergo serotonergic differentiation upon appropriate induction (4), we previously underlined the existence of functional interactions between three 5-HT receptor subtypes (5). Within 4 days of treatment with dibutyryl cyclic AMP and cyclohexane carboxylic acid, nearly 100% of 1C11 neuroprogenitor cells are converted into 1C11 5-HT neuronal cells, which express a complete serotonergic phenotype including 5-HT metabolism, storage, and transport (4). This serotonergic differentiation program is accompanied by the selective and time-dependent onset of three serotonergic receptors. 1C115-HT cells become sensitive to external 5-HT at day 2 of differentiation with the induction of 5-HT 1B/D (1500 GTI binding sites/cell) and 5-HT 2B

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“…Briefly, cell membranes were prepared by four cycles of homogenization (Brinkman P10 disrupter) and centrifugation (48,000 ϫ g for 15 min). The assay was established to achieve steady state conditions and to optimize specific binding (Kellermann et al, 1996). Fifty micrograms of membrane proteins were incubated with 5 nM [ 125 I]DOI at 4°C for 60 min.…”

Section: Binding Experimentsmentioning

confidence: 99%

Gain of affinity point mutation in the serotonin receptor gene 5‐HT_2Dro accelerates germband extension movements during Drosophila gastrulation

Schaerlinger

Launay

Vonesch

et al. 2007

Developmental Dynamics

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Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236:991-999, 2007.

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Sequential onset of three 5‐HT receptors during the 5‐hydroxytryptaminergic differentiation of the murine 1C11 cell line

Cited by 31 publications

References 34 publications

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein*

Gain of affinity point mutation in the serotonin receptor gene 5‐HT_2Dro accelerates germband extension movements during Drosophila gastrulation

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Sequential onset of three 5‐HT receptors during the 5‐hydroxytryptaminergic differentiation of the murine 1C11 cell line

Cited by 31 publications

References 34 publications

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein*

Gain of affinity point mutation in the serotonin receptor gene 5‐HT2Dro accelerates germband extension movements during Drosophila gastrulation

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Gain of affinity point mutation in the serotonin receptor gene 5‐HT_2Dro accelerates germband extension movements during Drosophila gastrulation