Reverse physiology in Drosophila: identification of a novel allatostatin-like neuropeptide and its cognate receptor structurally related to the mammalian somatostatin/galanin/opioid receptor family

Birgül, Necla; Weise, Christoph; Kreienkamp, Hans‐Jürgen; Richter, Dietmar

doi:10.1093/emboj/18.21.5892

Cited by 195 publications

(155 citation statements)

References 44 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…35 Recently, one of them (SRPYSFGLamide) was isolated from Drosophila in a reverse physiology experiment in which an orphan G protein coupled Drosophila receptor (GPCR), expressed in frog oocytes, was used to screen extracts for potential ligands. 36 Of the four predicted Drm-allatostatins, two could be detected both in the 1D and 2D LC/MS experiments: SRPYSFGLamide (Drm-allatostatin 3) and TTRPQPFNFGLamide (Drm-allatostatin 4). The third peptide, AYMYTNGGPGM, that could be identified by 1D LC/MS is absent in the 2D LC/MS read-outs.…”

Section: The Allatostatin Precursormentioning

confidence: 91%

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

et al. 2005

View full text Add to dashboard Cite

Peptides are the largest class of signalling molecules found in animals. Nevertheless, in most proteomic studies peptides are overlooked since they literally fall through the mazes of the net. In analogy with proteomics technology, where all proteins expressed in a cell or tissue are analyzed, the peptidomic approach aims at the simultaneous visualization and identification of the whole peptidome of a cell or tissue, i.e. all expressed peptides with their post-translational modifications. In this paper we describe the analysis of the larval fruit fly central nervous system using two-dimensional capillary liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF-MS/MS. Using the central nervous systems of only 50 larval Drosophila as starting material, we identified 38 peptides in a single analysis, 20 of which were not detected in a previous study that reported on the one-dimensional capillary LC/MS/MS analysis of the same tissue. Among the 38 sequenced peptides, some originate from precursors, such as the tachykinin and the IFamide precursor that were entirely missed in the first study. This clearly demonstrates that the two-dimensional capillary LC approach enhances the coverage of the peptidomic analysis.

show abstract

Section: The Allatostatin Precursormentioning

confidence: 91%

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

et al. 2005

View full text Add to dashboard Cite

show abstract

“…[ 35 S]GTP␥S Binding Assay-HEK-293 cells were transiently transfected by electroporation using 10 g of CG13803 per 4 ϫ 10 6 cells. Cells plated in 10-cm dishes were washed twice in phosphate-buffered saline and collected by cell scraper in ice-cold homogenization buffer (20 mM Tris-HCl (pH 7.4), 100 mM NaCl, 1 mM EDTA, 10 M GDP (Sigma), 1 mM phenylmethylsulfonyl fluoride, 1 tablet of protease inhibitor mixture (Roche Applied Science) per 10 ml) and were disrupted by a Dounce homogenizer.…”

Section: Methodsmentioning

confidence: 99%

Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

Johnson

Bohn

Barak

et al. 2003

Journal of Biological Chemistry

120

108

View full text Add to dashboard Cite

Activation of G protein-coupled receptors (GPCR)leads to the recruitment of ␤-arrestins. By tagging the ␤-arrestin molecule with a green fluorescent protein, we can visualize the activation of GPCRs in living cells. We have used this approach to de-orphan and study 11 GPCRs for neuropeptide receptors in Drosophila melanogaster. Here we verify the identities of ligands for several recently de-orphaned receptors, including the receptors for the Drosophila neuropeptides proctolin (CG6986), neuropeptide F (CG1147), corazonin (CG10698), dFMRF-amide (CG2114), and allatostatin C (CG7285 and CG13702). We also de-orphan CG6515 and CG7887 by showing these two suspected tachykinin receptor family members respond specifically to a Drosophila tachykinin neuropeptide. Additionally, the translocation assay was used to de-orphan three Drosophila receptors. We show that CG14484, encoding a receptor related to vertebrate bombesin receptors, responds specifically to allatostatin B. Furthermore, the pair of paralogous receptors CG8985 and CG13803 responds specifically to the FMRF-amide-related peptide dromyosuppressin. To corroborate the findings on orphan receptors obtained by the translocation assay, we show that dromyosuppressin also stimulated GTP␥S binding and inhibited cAMP by CG8985 and CG13803. Together these observations demonstrate the ␤-arrestin-green fluorescent protein translocation assay is an important tool in the repertoire of strategies for ligand identification of novel G protein-coupled receptors.

show abstract

“…More than 50 GPCRs resemble known receptors for known neuropeptide families based on phylogenetic comparisons with known vertebrate GPCRs (4). Of these GPCRs, based on sequence identity, C. elegans gene ZK455.3 expresses an nlp receptor, NPR-9, that is most similar to insect allatostatin/ mammalian galanin receptors (5)(6)(7)(8). Allatostatins are a family of neuropeptides that share a conserved C-terminal sequence -Tyr/PheXaaPheGlyLeu-NH 2 and are widespread throughout the invertebrate lineage (9,10).…”

mentioning

confidence: 99%

A Caenorhabditis elegans allatostatin/galanin-like receptor NPR-9 inhibits local search behavior in response to feeding cues

Bendena

Boudreau

Papanicolaou

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Movement inCaenorhabditis elegans is the result of sensory cues creating stimulatory and inhibitory output from sensory neurons. Four interneurons (AIA, AIB, AIY, and AIZ) are the primary recipients of this information that is further processed en route to motor neurons and muscle contraction. C. elegans has >1,000 G proteincoupled receptors (GPCRs), and their contribution to sensory-based movement is largely undefined. We show that an allatostatin/ galanin-like GPCR (NPR-9) is found exclusively in the paired AIB interneuron. AIB interneurons are associated with local search/ pivoting behavior. npr-9 mutants display an increased local search/ pivoting that impairs their ability to roam and travel long distances on food. With impaired roaming behavior on food npr-9 mutants accumulate more intestinal fat as compared with wild type. Overexpression of NPR-9 resulted in a gain-of-function phenotype that exhibits enhanced forward movement with lost pivoting behavior off food. As such the animal travels a great distance off food, creating arcs to return to food. These findings indicate that NPR-9 has inhibitory effects on the AIB interneuron to regulate foraging behavior, which, in turn, may affect metabolic rate and lipid storage.neuropeptide receptor ͉ nerve transmission ͉ foraging ͉ glutamate receptor ͉ interneuron A major challenge in neurobiology is to understand the control of behavior at the molecular level. Neuropeptides and their receptors offer promising candidates for the regulation of various behaviors and changes in physiology. The Caenorhabditis elegans genome sequence has allowed the identification of 109 putative neuropeptide genes encoding precursors that may be processed to Ϸ250 neuropeptides (1-3). These neuropeptides are grouped into three families: FMRFamide-related peptides (f lp), insulin-like peptides (ins), and neuropeptide-like-peptides (nlps). C. elegans expresses Ͼ1,000 orphan G protein-coupled receptors (GPCRs). More than 50 GPCRs resemble known receptors for known neuropeptide families based on phylogenetic comparisons with known vertebrate GPCRs (4). Of these GPCRs, based on sequence identity, C. elegans gene ZK455.3 expresses an nlp receptor, NPR-9, that is most similar to insect allatostatin/ mammalian galanin receptors (5-8). Allatostatins are a family of neuropeptides that share a conserved C-terminal sequence -Tyr/PheXaaPheGlyLeu-NH 2 and are widespread throughout the invertebrate lineage (9, 10). In insects, allatostatins regulate numerous physiological functions, including inhibition of juvenile hormone biosynthesis (11, 12), inhibition of muscle contraction (13), myoendocrine regulation (14, 15), neuromodulation (16), and regulation of enzymatic activities (17) and ecdysis (18). Similarly, mammalian galanin modulates a wide variety of processes that range from neurotransmission, nociception, feeding and metabolism, energy and osmotic homeostasis and learning and memory (19). We report that NPR-9 is uniquely localized in interneuron AIB to negatively regulate a variety of inputs th...

show abstract

Reverse physiology in Drosophila: identification of a novel allatostatin-like neuropeptide and its cognate receptor structurally related to the mammalian somatostatin/galanin/opioid receptor family

Cited by 195 publications

References 44 publications

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

A Caenorhabditis elegans allatostatin/galanin-like receptor NPR-9 inhibits local search behavior in response to feeding cues

Contact Info

Product

Resources

About