<i>Drosophila CG8422</i>encodes a functional diuretic hormone receptor

Johnson, Erik C.; Bohn, Laura M.; Taghert, Paul H.

doi:10.1242/jeb.00818

Cited by 100 publications

(77 citation statements)

References 41 publications

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“…2). We previously reported that HEK293 cells transfected with DH44-R1 were two orders of magnitude more sensitive to DH 44 stimulation (Johnson et al, 2004), and repeated those experiments here and estimate a similar EC 50 value (5.12E-09 mol l -1 ) in the nanomolar range (Fig. 2).…”

Section: Resultssupporting

confidence: 84%

“…Previous studies have shown that DH 44 application to isolated tubules leads to elevated cAMP levels (Cabrero et al, 2002), and that the CG12370-related receptor, DH44-R1, encoded by CG8422, has been shown to stimulate this second messenger system as well (Johnson et al, 2004). Based on these observations, we tested for possible changes in this specific signaling component on HEK293 cells expressing CG12370.…”

Section: Resultsmentioning

confidence: 93%

“…DH44-R1 had previously been found to increase intracellular calcium levels, whereas DH 44 stimulation of Malpighian tubules failed to do so (Johnson et al, 2004;Cabrero et al, 2002). Using SRE-luc as an indicator of calcium levels, we found that 10 -6 mol l To confirm that DH 44 was leading to activation of the CG12370, we examined microscopically the distribution of a β-arrestin-GFP fusion protein, which translocates from the cytoplasm to the plasma membrane upon receptor stimulation.…”

Section: Resultsmentioning

confidence: 96%

“…Congruent with results on this peptide in tubule assays (Coast et al, 2001), this receptor is expressed in the principal cells of the tubule and elevates intracellular cAMP levels . The DH 44 peptide binds to the receptor encoded by CG8422 (DH44-R1) (Johnson et al, 2004); however, the sensitivity of this receptor for DH 44 was two orders of magnitude greater than values for DH 44 peptide sensitivity derived at the tubule (Cabrero et al, 2002). Also, this receptor was found to activate both cAMP and Ca 2+ levels in HEK293 cells (Johnson et al, 2004), whereas DH 44 was found to only increase cAMP levels in explanted tubules (Cabrero et al, 2002).…”

Section: Introductionmentioning

confidence: 91%

“…The DH 44 peptide binds to the receptor encoded by CG8422 (DH44-R1) (Johnson et al, 2004); however, the sensitivity of this receptor for DH 44 was two orders of magnitude greater than values for DH 44 peptide sensitivity derived at the tubule (Cabrero et al, 2002). Also, this receptor was found to activate both cAMP and Ca 2+ levels in HEK293 cells (Johnson et al, 2004), whereas DH 44 was found to only increase cAMP levels in explanted tubules (Cabrero et al, 2002). Notably, DH44-R1 has a receptor paralog, encoded by CG12370 (Hewes and Taghert, 2001), which, based on the high degree of sequence similarity, is predicted to be an additional target of DH 44 activation.…”

Section: Introductionmentioning

confidence: 91%

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Functional differences between two CRF-related diuretic hormone receptors in Drosophila

Hector

Bretz

Zhao

et al. 2009

Journal of Experimental Biology

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SUMMARYIn Drosophila, two related G-protein-coupled receptors are members of the corticotropin releasing factor (CRF) receptor subfamily. We have previously reported that one of these receptors, encoded by CG8422 is a functional receptor for a diuretic hormone, DH 44 . Here, we report that the other CRF receptor subfamily member, encoded by CG12370, is also a receptor for the DH 44 neuropeptide. The lines of evidence to support this identification include increases in cAMP levels due to CG12370 receptor activation and the recruitment of β-arrestin-GFP to the plasma membrane in response to DH 44 application. We compared these features of the receptors DH44-R2 (encoded by CG12370) and DH44-R1 (encoded by CG8422) and found fundamental differences in signaling, association with the arrestins, and peptide sensitivity. We found that the sensitivity of DH44-R2 to the DH 44 peptide is lower than that of DH44-R1, specifically an estimated EC 50 of 7.98E-07 mol l -1 for DH 44 by DH44-R2 to an EC 50 of 5.12E-09 mol l -1 by DH44-R1 and found that previous reports on the sensitivity of the tubule to DH 44 is in agreement with our measurements of DH44-R2 sensitivity. We employed a specific RNAi construct to selectively knock-down DH44-R2 expression and this led to heightened sensitivity to osmotic challenges. The functional characterization of this diuretic hormone receptor in Drosophila demonstrates a high degree of conservation of CRF-like signaling.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 91%

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Functional differences between two CRF-related diuretic hormone receptors in Drosophila

Hector

Bretz

Zhao

et al. 2009

Journal of Experimental Biology

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Widely distributedDrosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides

et al. 2005

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Neuropeptides related to vertebrate tachykinins have been identified in Drosophila. Two Drosophila G-protein-coupled receptors (GPCRs), designated NKD (CG6515) and DTKR (CG7887), cloned earlier, display sequence similarities to mammalian tachykinin receptors. However, they were not characterized with the endogenous Drosophila tachykinins (DTKs). The present study characterizes one of these receptors, DTKR. We determined that HEK-293 cells transfected with DTKR displayed dose-dependent increases in both intracellular calcium and cyclic AMP levels in response to the different DTK peptides. DTK peptides also induced internalization of DTKR-green fluorescent protein (GFP) fusion constructs in HEK-293 cells. We generated specific antireceptor antisera and showed that DTKR is widely distributed in the adult brain and more scarcely in the larval CNS. The distribution of the receptor in brain neuropils corresponds well with the distribution of its ligands, the DTKs. Our findings suggest that DTKR is a DTK receptor in Drosophila and that this ligand-receptor system plays multiple functional roles.

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Neuropeptide Biology in Drosophila

Clynen

Reumer

Baggerman

et al. 2010

Advances in Experimental Medicine and Biology

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Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/modulators and hormones. By means of bioinformatics 119 (neuro)peptide precursor genes have been predicted from the Drosophila genome. Using the neuropeptidomics technology 46 neuropeptides derived from 19 of these precursors could be biochemically characterized. At the cellular level, neuropeptides usually exert their action by binding to membrane receptors, many of which belong to the family of G-protein coupled receptors or GPCRs. Such receptors are the major target for many contemporary drugs. In this chapter, we will describe the identification, localization and functional characterization of neuropeptide-receptor pairs in Drosophila melanogaster. Introduction: Drosophila as a Model to Study Neuropeptide SignalingDrosophila has revolutionized biology more than any other organism. The entire genus contains about 1,500 species and is very diverse in appearance, behavior and breeding habitat. One species in particular, Drosophila melanogaster, has been heavily used in research in genetics and developmental biology. Also for neuropeptide research Drosophila is a very suitable model organism, especially since its genome has been nearly fully sequenced and is publicly accessible. 1 Neuropeptides form the largest class of signaling molecules in animals. They transmit and regulate bio-information in the circulatory as well as the neuronal system and exert their role mostly by acting on G-protein coupled receptors or GPCRs. As such, neuropeptides play critical roles in regulating most biological processes. Neuropeptides are diverse in structure, localization and function. Their only common feature is that they are all synthesized as peptide precursor proteins, also called preproproteins. Besides the neuropeptides themselves, also the receptors they act on are structurally diverse and the resulting signaling cascades are also highly varied, so there is a tremendous potential of different effects on living cells. Therefore, peptides are attractive for pharmaceutical and agro-industrial companies because they represent (lead) compounds that can be further exploited for diverse practical applications. Peptides as such cannot be used as therapeutics or as insecticides, because they are usually broken down before they reach their target. Therefore, small compounds called peptidomimetics that mimic or block the interaction of the peptide with its receptor are being developed. As more genomes become available, the findings in Drosophila can be readily expanded to other species, including those of economic interest.

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Drosophila CG8422encodes a functional diuretic hormone receptor

Cited by 100 publications

References 41 publications

Functional differences between two CRF-related diuretic hormone receptors in Drosophila

Functional differences between two CRF-related diuretic hormone receptors in Drosophila

Widely distributedDrosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides

Neuropeptide Biology in Drosophila

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