Cloning and characterization of a Drosophila tyramine receptor.

Saudou, Frédéric; Amlaiky, N.; Plassat, Jean‐Luc; Borrelli, Emiliana; Hen, R.

doi:10.1002/j.1460-2075.1990.tb07572.x

Cited by 240 publications

(231 citation statements)

References 28 publications

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“…The splice variant (ser-2a) lacks 69 nucleotides from exon 7, which corresponds to a 23 amino acid deletion in the third intracellular loop. The predicted amino acid sequences of ser-2 and ser-2a contain motifs characteristic of the biogenic amine GPCR family and, in particular, greatest identity to insect TA/OA receptors (Saudou et al 1990;Vanden Broeck et al 1995;Blenau et al 2000). SER-2 clusters with insect TA/OA receptors that couple to G ai/o that inhibit adenylyl cyclase activity (Blenau et al 2000;Saudou et al 1990;Vanden Broeck et al 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The predicted amino acid sequences of ser-2 and ser-2a contain motifs characteristic of the biogenic amine GPCR family and, in particular, greatest identity to insect TA/OA receptors (Saudou et al 1990;Vanden Broeck et al 1995;Blenau et al 2000). SER-2 clusters with insect TA/OA receptors that couple to G ai/o that inhibit adenylyl cyclase activity (Blenau et al 2000;Saudou et al 1990;Vanden Broeck et al 1995). Significantly, TA reduced forskolin-stimulated cAMP levels in HEK293 cells stably expressing SER-2 with an IC 50 of about 363 nM, further supporting the characterization of SER-2 as a TA receptor.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a tyramine receptor from Caenorhabditis elegans

Rex

Komuniecki

2002

Journal of Neurochemistry

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Octopamine (OA) plays an important role in the regulation of a number of key processes in nematodes, including pharyngeal pumping, locomotion and egg-laying. However, while putative OA receptors can be tentatively identified in the Caenorhabditis elegans database, no OA receptors have been functionally characterized from any nematode. We have isolated two cDNAs, ser-2 and ser-2a, encoding putative C. elegans serotonin/OA receptors (C02D4.2, ser-2). The sequences of these cDNAs differ from that predicted by GeneFinder and lack 42 bp of exon 2. In addition, ser-2a appears to be alternatively spliced and lacks a predicted 23 amino acids in the third intracellular loop. COS-7 cells expressing SER-2 bind [ 3 H]LSD in the low nM range and exhibit K i s for tyramine, octopamine and serotonin of 0.07, 2, and 13.7 lM, respectively. Significantly, tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells stably expressing SER-2 with an IC 50 of about 360 nM, suggesting that SER-2 is a tyramine receptor. Keywords: Caenorhabditis elegans, cyclic AMP, G-protein coupled receptor, tyramine. Understanding the signaling pathways involved in key nematode-specific processes, such as locomotion, pharyngeal pumping and egg laying, may aid in the identification of novel targets for the development of new classes of anthelmintics. The biogenic amine octopamine (OA) is a neuroactive ligand in many invertebrates and appears to play an important role in nematode physiology. The biosynthesis of OA requires the hydroxylation of tyramine (TA) to OA by tyramine b-hydroxylase and the effects of OA and TA are mediated by G-protein coupled receptors, many of which positively or negatively modulate adenylyl cyclase activity (Roeder 1999). Studies on the physiological role and signaling of OA and its precursor TA have focused largely on insects where, OA and TA regulate a variety of processes, including energy generation via fat body metabolism (Downer 1979;Wang et al. 1990;Blau and Wegener 1994;Park and Keeley 1998), regulation of egg-laying (Monastirioti et al. 1996;Torfs et al. 2000) and induction of feeding (Braun and Bicker 1992). The role of TA and OA in mammals is not well studied but has recently gained much attention due to the isolation of human and rodent receptors that specifically bind TA and couple to G as , highlighting the need to re-evaluate the role of these trace amines in vertebrates (Borowsky et al. 2001).In the free-living nematode, Caenorhabditits elegans, a putative tyramine-b hydroxylase (tbh-1) has been identified and localized to the two RIC interneurons, suggesting they are octopaminergic (Alkema and Horvitz, personal communication). Mutants lacking tbh-1 move more slowly than wild type, indicating a role for OA in locomotion. Indeed, ectopic application of OA to wild type C. elegans enhances locomotion and inhibits pharyngeal pumping and egg laying (Horvitz et al. 1982). Significantly, the inhibition of pharyngeal pumping induced by OA in C. elegans appears to be mediated by G ao . OA inhibits the fir...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of a tyramine receptor from Caenorhabditis elegans

Rex

Komuniecki

2002

Journal of Neurochemistry

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“…Six months later Saudou et al (1990) reported the success of their cloning efforts using degenerate oligonulceotide probes based on conserved amino acid residues present in the highly conserved, putative transmembrane domains VI and VII of several biogenic amine responsive vertebrate receptors. The cDNA they identified turned out to code for a GPCR identical to the one reported by Arakawa et al (1990).…”

Section: Invertebrate Trace Amine-activated Receptorsmentioning

confidence: 99%

Trace amine-associated receptor 1—Family archetype or iconoclast?

Grandy

2007

Pharmacology & Therapeutics

173

209

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Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the 'trace amines' (TAs) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of two publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers as TA1 (Borowsky et al., 2001) and TAR1 (Bunzow et al., 2001). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines recombinant rodent and human TA receptors dosedependently couple to the stimulation of cAMP production. Structure-activity profiling based on this functional response has revealed that in addition to the TAs, other biologically active compounds containing a 2 carbon aliphatic side chain linking an amino group to at least one benzene ring are potent and efficacious TA receptor agonists with amphetamine, methamphetamine, 3-iodothyronamine, thyronamine, and dopamine among the most notable. Almost 100 years after the search for TA receptors began numerous TA1/TAR1-related sequences, now called Trace AmineAssociated Receptors (TAARs), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TA receptor a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCRs. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

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“…Classically, biogenic amines including 5-HT bind to amino acid side chains within the transmembrane domains of their receptors (Manivet et al, 2002). However, in Drosophila, most biogenic amine receptors have a long N-terminal domain (Onai et al, 1989;Saudou et al, 1990;Witz et al, 1990;Colas et al, 1995;Gotzes and Baumann, 1996). Few studies have been performed to understand the role of these long domains.…”

Section: Mutation In the N-terminal Domain Of 5-ht 2dro Receptor Is Amentioning

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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Cloning and characterization of a Drosophila tyramine receptor.

Cited by 240 publications

References 28 publications

Characterization of a tyramine receptor from Caenorhabditis elegans

Characterization of a tyramine receptor from Caenorhabditis elegans

Trace amine-associated receptor 1—Family archetype or iconoclast?

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

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Cloning and characterization of a Drosophila tyramine receptor.

Cited by 240 publications

References 28 publications

Characterization of a tyramine receptor from Caenorhabditis elegans

Characterization of a tyramine receptor from Caenorhabditis elegans

Trace amine-associated receptor 1—Family archetype or iconoclast?

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