<i>Drosophila</i> molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2

Mendive, Fernando; Loy, Tom Van; Claeysen, Sylvie; Poels, Jeroen; Williamson, Michael; Hauser, Frank; Grimmelikhuijzen, Cornelis J.P.; Vassart, Gilbert; Broeck, Jozef Vanden

doi:10.1016/j.febslet.2005.03.006

Cited by 141 publications

(156 citation statements)

References 34 publications

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“…RT-PCR analysis of the house fly bursicon α and β genes in the CNS reveals that both bursicon α and β genes were transcribed as early as in the first instar larvae, reached the maximum levels in pharate adult, and declined sharply after adult emergence. The sharp decline of the bursicon α and β transcripts after adult emergence observed in the house fly CNS is in agreement with the reports in Drosophila (Luo et al, 2005;Mendive et al, 2005) and in B. mori (Huang et al, 2007), indicating active translation and release of bursicon into hemolymph for cuticle sclerotization of the newly emerged fly. The developmental profiles of bursicon α and β transcripts at the larval and pupal stages of the house fly show a relatively steady increase with a little fluctuation while a big fluctuation of bursicon α and β transcripts has been reported at the larval and pupal stages of Drosophila (Luo et al, 2005;Mendive et al, 2005).…”

Section: Discussionsupporting

confidence: 91%

“…DLGR2, once activated, is hypothesized to activate the cAMP/PKA signaling pathway (Kimura et al, 2004). It has now been shown that the recombinant bursicon heterodimer binds to and activates DLGR2, which in turn leads to dose-dependent intracellular increase in adenyl cyclase activity and cAMP production in the mammalian 293T cells and COS-7 cells that over-express DLGR2 (Luo et al, 2005;Mendive et al, 2005). A gene-silencing study reveals that injection of the double-stranded bursicon α RNA into B. mori pupae significantly reduces the level of bursicon α mRNA in pupae, resulting in a deficit in wing expansion in adults (Huang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional expression of bursicon and novel bursicon‐regulated genes in the house fly Musca domestica

Wang

Song

2008

Arch Insect Biochem Physiol

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Bursicon is a neuropeptide that regulates cuticle sclerotization (hardening and tanning) via a G protein-coupled receptor. It consists of two subunits, an alpha and a beta. In the present study, we investigated the transcriptional expression and in situ localization of bursicon α and β in the central nerve system of the house fly Musca domestica. Most importantly, we identified two novel bursicon-regulated genes using recombinant bursicon (rbursicon) heterodimer in a neck-ligated house fly assay. RT-PCR analysis revealed that both bursicon α and β subunits were present in the central nerve system of larval and pupal stages, reached the maximal level in pharate adults, and declined sharply after adult emergence, suggesting the release of the hormone upon adult emergence. In situ localization of bursicon transcripts showed that both bursicon α and β transcripts were expressed in a set of neurosecretory cells (NSCs) in the thoracic-abdominal ganglia of M. domestica. Two Drosophila melanogaster homologous genes, designated CG7985hh and CG30287hh, were up-regulated by rbursicon in a time-dependent manner and verified by real-time PCR, implying their involvement in the cuticle tanning process. Arch. Insect

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Transcriptional expression of bursicon and novel bursicon‐regulated genes in the house fly Musca domestica

Wang

Song

2008

Arch Insect Biochem Physiol

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“…The ␣-and ␤-subunits of bursicon have also been called bursicon and partner-of-bursicon ( pburs) (Luo et al, 2005). To avoid ambiguity between the subunit names and the name of the active hormone, which is a dimer of both subunits, we follow the nomenclature of Mendive et al (2005) in calling the subunit encoded by CG13419 the ␣-subunit and the subunit encoded by CG15284 the ␤-subunit. We refer to the antibodies specific for the two subunits antiburs␣ and anti-burs␤, respectively.…”

Section: Methodsmentioning

confidence: 99%

Functional Dissection of a Neuronal Network Required for Cuticle Tanning and Wing Expansion inDrosophila

Luan¹,

Lemon²,

Peabody³

et al. 2006

J. Neurosci.

177

238

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A subset of Drosophila neurons that expresses crustacean cardioactive peptide (CCAP) has been shown previously to make the hormone bursicon, which is required for cuticle tanning and wing expansion after eclosion. Here we present evidence that CCAP-expressing neurons (N CCAP ) consist of two functionally distinct groups, one of which releases bursicon into the hemolymph and the other of which regulates its release. The first group, which we call N CCAP -c929, includes 14 bursicon-expressing neurons of the abdominal ganglion that lie within the expression pattern of the enhancer-trap line c929-Gal4. We show that suppression of activity within this group blocks bursicon release into the hemolymph together with tanning and wing expansion. The second group, which we call N CCAP -R, consists of N CCAP neurons outside the c929-Gal4 pattern. Because suppression of synaptic transmission and protein kinase A (PKA) activity throughout N CCAP , but not in N CCAP -c929, also blocks tanning and wing expansion, we conclude that neurotransmission and PKA are required in N CCAP -R to regulate bursicon secretion from N CCAP -c929. Enhancement of electrical activity in N CCAP -R by expression of the bacterial sodium channel NaChBac also blocks tanning and wing expansion and leads to depletion of bursicon from central processes. NaChBac expression in N CCAP -c929 is without effect, suggesting that the abdominal bursicon-secreting neurons are likely to be silent until stimulated to release the hormone. Our results suggest that N CCAP form an interacting neuronal network responsible for the regulation and release of bursicon and suggest a model in which PKA-mediated stimulation of inputs to normally quiescent bursicon-expressing neurons activates release of the hormone.

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“…These are themselves part of a subfamily of receptors characterized by an ectodomain containing leucine-rich repeat motifs (LRRs), in addition to the canonical heptahelical serpentine domain typical of GPCRs. They are called leucine repeat-containing receptors (LGRs) (Hsu et al 2000) and contain the recently identified relaxin (LGR7) (Hsu et al 2002) and insulin-like 3 receptors (LGR8) (Kumagai et al 2002) together with the receptor to the insect melanizing hormone bursicon (DLGR2) (Luo et al 2005, Mendive et al 2005) and orphan receptors.…”

Section: Introductionmentioning

confidence: 99%

Specificity and promiscuity of gonadotropin receptors

Costagliola

Urizar²,

Mendive³

et al. 2005

Reproduction

Self Cite

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The dichotomy between hormone recognition by the ectodomain and activation of the G protein by the rhodopsin-like serpentine portion is a well established property of glycoprotein hormone receptors. The specificity barrier avoiding promiscuous activation of the FSH receptor by the high concentration of human chorionic gonadotropin (hCG) prevailing during human pregnancy was thus believed to lie in the ectodomain. In the past two years, mutations responsible for rare spontaneous cases of ovarian hyperstimulation syndromes have partially modified this simple view. Five naturally occurring mutations have been identified which cause an increase in the sensitivity of the FSH receptor to hCG. Surprisingly, these mutations are all located in the serpentine portion of the receptor. In addition to their effect on sensitivity to hCG, they increase sensitivity of the FSH receptor to TSH, and are responsible for activating the receptor constitutively. Together, the available information indicates that the ectodomain and the serpentine domain of the FSH receptor each contribute to the specificity barrier preventing its spurious activation by hCG. While the former is responsible for establishment of binding specificity, the latter introduces a novel notion of functional specificity. Recent data demonstrate that LH and FSH receptors can constitute functional homo-and heterodimers. This suggests the possibility that in cells co-expressing the two receptors, such as granulosa cells, the heterodimers might be endowed with functional characteristics different from those of each homodimer.

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Drosophila molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2

Cited by 141 publications

References 34 publications

Transcriptional expression of bursicon and novel bursicon‐regulated genes in the house fly Musca domestica

Transcriptional expression of bursicon and novel bursicon‐regulated genes in the house fly Musca domestica

Functional Dissection of a Neuronal Network Required for Cuticle Tanning and Wing Expansion inDrosophila

Specificity and promiscuity of gonadotropin receptors

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