Drosophila 5-HT2 serotonin receptor: coexpression with fushi-tarazu during segmentation.

Abstract

Serotonin, first described as a neurotransmitter in invertebrates, has been investigated mostly for its functions in the mature central nervous system of higher vertebrates. Serotonin receptor diversity has been described in the mammalian brain and in insects. We report the isolation of a cDNA coding for a Drosophila melanogaster serotonin receptor that displays a sequence, a gene organization, and pharmacological properties typical of the mammalian 5-HT2 serotonin receptor subtype. Its mRNA can be detected in the adult fly; moreover, a high level of expression occurs at 3 hr ofDrosophila embryogenesis. This early embryonic expression is surprisingly organized in a seven-stripe pattern that appears at the cellular blastoderm stage. In addition, this pattern is in phase with that of the even-parasegment-expressed pair-rule gene fushi-tarazu and is similarly modified by mutations affecting segmentation genes. Simultaneously with this pair-rule expression, the complete machinery of serotonin synthesis is present and leads to a peak of ligand concomitant with a peak of 5-HT2-specific receptor sites in blastoderm embryos.In vertebrates, the biogenic amine serotonin (5-hydroxytryptamine, 5-HT) affects a wide variety of behavioral and physiological functions that are mediated by numerous receptor subtypes. These receptors can be classified according to the transduction mechanisms: the 5-HT1 subtype as an adenylyl cyclase inhibitor, 5-HT2 as a phospholipase C stimulator, and 5-HT4, 5-HT6, and 5-HT7 as adenylyl cyclase activators; these are all G protein-coupled receptors. The 5-HT3 subtype is a ligand-gated channel (1). In insects, biogenic amines are similarly implicated as neuromodulators and neurotransmitters (2) in addition to their function of crosslinking proteins and chitin during sclerotization of the cuticle (3). In Drosophila melanogaster, the serotoninergic neurons have been localized (4) and implicated in salivary gland secretion, heart and oviduct contractions, circadian rhythms, and learning and memory (2). 5-HT receptors have also been detected as a heterogeneous population by[3H]5-HT binding experiments or by second-messenger cou-

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

“…The gene encoding this receptor is localized on the right arm of the third chromosome at 82C5 (Colas et al, 1995). Using EMS, Meagraw and Kaufman (FlyBase) screened several homozygous lethal mutants in the 82C4-D5 region.…”

“…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.…”

“…[ 125 I]DOI was used as a radioligand to investigate the pharmacological properties of membrane fractions from 5-HT 2Dro R transiently transfected COS-1 cells (Colas et al, 1995). Briefly, cell membranes were prepared by four cycles of homogenization (Brinkman P10 disrupter) and centrifugation (48,000 ϫ g for 15 min).…”

“…In Drosophila, four 5-HT receptors have been described (Witz et al, 1990;Saudou et al, 1992;Colas et al, 1995) in addition to the transporter (Park et al, 2006).…”

“…Further experiments demonstrated that the 5-HT 2Dro receptor is functional during early developmental stages. Concomitant with 5-HT 2Dro receptor expression, there is also a detectable transient peak of 5-HT synthesis (Colas et al, 1995). Moreover, the 5-HT 2Dro receptor mRNA is expressed in a pattern similar to the pair-rule gene Fushi tarazu (Pankratz and Jä ckle, 1993).…”