Advertisement
JOURNAL ARTICLES
The Drosophila G-protein-coupled receptor kinase homologue Gprk2 is required for egg morphogenesis
L.E. Schneider, A.C. Spradling
Development 1997 124: 2591-2602;

Summary

G protein signaling is a widely utilized form of extracellular communication that is mediated by a family of serpentine receptors containing seven transmembrane domains. In sensory neurons, cardiac muscle and other tissues, G protein-coupled receptors are desensitized through phosphorylation by a family of kinases, the G protein-coupled receptor kinases (GRKs). Desensitization allows a cell to decrease its response to a given signal, in the continued presence of that signal. We have identified a Drosophila mutant, gprk2(6936) that disrupts expression of a putative member of the GRK family, the G protein-coupled receptor kinase 2 gene (Gprk2). This mutation affects Gprk2 gene expression in the ovaries and renders mutant females sterile. The mutant eggs contain defects in several anterior eggshell structures that are produced by specific subsets of migratory follicle cells. In addition, rare eggs that become fertilized display gross defects in embryogenesis. These observations suggest that developmental signals transduced by G protein-coupled receptors are regulated by receptor phosphorylation. Based on the known functions of G protein-coupled receptor kinases, we speculate that receptor desensitization assists cells that are migrating or undergoing shape changes to respond rapidly to changing external signals.

REFERENCES

    1. Alcedo J.,
    2. Ayzenzon M.,
    3. von Ohlen T.,
    4. Noll M.,
    5. Hooper J. E.
    (1996) The Drosophilasmoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell 86, 221–232
    OpenUrlCrossRefPubMedWeb of Science
    1. Arakawa S.,
    2. Gocayne J. D.,
    3. McCombie W. R.,
    4. Urquhart D. A.,
    5. Hall L. M.,
    6. Fraxer C. M.,
    7. Venter J. C.
    (1990) Cloning, localization, and permanent expression of a Drosophila octopamine receptor. Neuron 2, 343–354
    1. Bellen H. J.,
    2. Gregory B. K.,
    3. Oslo C. L.,
    4. Kiger J. A., Jr
    (1987) Two Drosophila learning mutants, dunce and rutabaga, provide evidence of a maternal role for cAMP on embryogenesis. Dev. Biol 121, 432–444
    OpenUrlCrossRefPubMedWeb of Science
    1. Benovic J. L.,
    2. DeBlasi A.,
    3. Stone W. C.,
    4. Caron M. G.,
    5. Lefkowitz R. J.
    (1986) -adrenergic receptor kinase: Identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc. Natl. Acad. Sci. USA 83, 2797–2801
    OpenUrlAbstract/FREE Full Text
    1. Bhanot P.,
    2. Brink M.,
    3. Harryman Samos C.,
    4. Hsieh J.-C.,
    5. Wang Y.,
    6. Macke J. P.,
    7. Andrew D.,
    8. Nathans J.,
    9. Nusse R.
    (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225–230
    OpenUrlCrossRefPubMedWeb of Science
    1. Birnbaumer L.
    (1992) Receptor-to-effector signaling through G proteins: Roles fordimers as well as subunits. Cell 71, 1069–1972
    OpenUrlCrossRefPubMedWeb of Science
    1. Blackman R. K.,
    2. Sanicola M.,
    3. Raftery L. A.,
    4. Gillevet T.,
    5. Gelbart W. M.
    (1991) An extensive 3cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-family in Drosophila. Development 111, 657–666
    OpenUrlAbstract
    1. Blair S. S.
    (1992) engrailed expression in the anterior lineage compartment of the developing wing blade of Drosophila. Development 115, 21–33
    OpenUrlAbstract
    1. Brown J. H.,
    2. Kafatos F. C.
    (1988) Functional libraries from Drosophila embryos. J. Molec. Biol 203, 425–437
    OpenUrlCrossRefPubMedWeb of Science
    1. Cassill J. A.,
    2. Whitney M.,
    3. Joazeiro A. P.,
    4. Becker A.,
    5. Zuker C. S.
    (1991) Isolation of Drosophila genes encoding G protein-coupled receptor kinases. Proc. Natl. Acad. Sci. USA 88, 11067–11070
    OpenUrlAbstract/FREE Full Text
    1. Colas J. F.,
    2. Launay J. M.,
    3. Kellermann O.,
    4. Rosay P.,
    5. Maroteaux L.
    (1995) Drosophila 5-HT2 serotonin receptor: Coexpression with fushi-tarazu during segmentation. Proc. Natl. Acad. Sci. USA 92, 5441–5445
    OpenUrlAbstract/FREE Full Text
    1. Cooley L.,
    2. Kelley R.,
    3. Spradling A. C.
    (1988) Insertional mutagenesis of the Drosophila genome with single P elements. Science 239, 1121–1128
    OpenUrlAbstract/FREE Full Text
    1. Davis R. L.,
    2. Cherry J.,
    3. Dauwalder B.,
    4. Han P. L.,
    5. Skoulakis E.
    (1995) The cyclic AMP system and Drosophila learning. Mol. Cell. Biochem 149, 271–278
    1. de Belle J. S.,
    2. Heisenberg M.
    (1994) Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. Science 263, 692–695
    OpenUrlAbstract/FREE Full Text
    1. Devreotes P. N.
    (1994) G protein-linked signaling pathways control the developmental program of Dictyostelium. Neuron 12, 235–241
    OpenUrlCrossRefPubMedWeb of Science
    1. Forbes A. J.,
    2. Lin H.,
    3. Ingham P. W.,
    4. Spradling A. C.
    (1996) hedgehog is required for the proliferation and specification of ovarian somatic cells prior to egg chamber formation in Drosophila. Development 122, 1125–1135
    OpenUrlAbstract
    1. Forbes A. J.,
    2. Spradling A. C.,
    3. Ingham P. W.,
    4. Lin H.
    (1996) The role of segment polarity genes during early oogenesis in Drosophila. Development 122, 3283–3294
    OpenUrlAbstract
    1. Fredericks Z. L.,
    2. Pitcher J. A.,
    3. Lefkowitz R. J.
    (1996) Identification of the G protein-coupled receptor kinase phosphorylation sites in the human2-adrenergic receptor. J. Biol. Chem 271, 13796–13803
    OpenUrlCrossRefPubMedWeb of Science
    1. Garland A. M.,
    2. Grady E. F.,
    3. Lovett M.,
    4. Vigna S. R.,
    5. Frucht M. M.,
    6. Krause J. E.,
    7. Bunnett N. W.
    (1996) Mechanisms of desensitization and resensitization of G protein-coupled neurokinin1 and neurokinin2 receptors. Mol. Pharmacol 49, 438–446
    OpenUrlAbstract
    1. Gilman A. G.
    (1987) G proteins: Transducers of receptor-generated signals. Ann. Rev. Biochem 56, 615–649
    OpenUrlCrossRefPubMedWeb of Science
    1. Gotzes F.,
    2. Balfanz S.,
    3. Baumann A.
    (1994) Primary structure andfunctional characterization of a Drosophila dopamine receptor with high homology to human D1/5 receptors. Recept. Channels 2, 131–141
    OpenUrlPubMedWeb of Science
    1. Hafner S.,
    2. Adler H. S.,
    3. Mischak H.,
    4. Janosch P.,
    5. Heidecker G.,
    6. Wolfman A.,
    7. Pippig S.,
    8. Lohse M.,
    9. Ueffing M.,
    10. Kolch W.
    (1994) Mechanism of inhibition of Raf-1 by protein kinase A. Mol. Cell. Biol 14, 6696–6703
    OpenUrlAbstract/FREE Full Text
    1. Han K. A.,
    2. Millar N. S.,
    3. Grotewiel M. S.,
    4. Davis R. L.
    (1996) DAMB, a novel dopamine receptor expressed specifically in Drosophila mushroom bodies. Neuron 16, 1127–1135
    OpenUrlCrossRefPubMedWeb of Science
    1. Heisenberg M.,
    2. Borst A.,
    3. Wagner S.,
    4. Byers D.
    (1985) Drosophila mushroom body mutants are deficient in olfactory learning. J. Neurogen 2, 1–30
    OpenUrlCrossRefPubMedWeb of Science
    1. Horowitz H.,
    2. Berg C. A.
    (1995) Aberrant splicing and transcription termination caused by P element insertion into the intron of a Drosophila gene. Genetics 139, 327–335
    OpenUrlAbstract/FREE Full Text
    1. Ingham P. W.
    (1995) Signaling by hedgehog family proteins in Drosophila and vertebrate development. Curr. Opin.Genet. Dev 5, 528–534
    OpenUrl
    1. Jiang J.,
    2. Struhl G.
    (1995) Protein kinase A and hedgehog signaling in Drosophila limb development. Cell 80, 563–.
    OpenUrlCrossRefPubMedWeb of Science
    1. Karpen G. H.,
    2. Spradling A. C.
    (1992) Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P-element insertional mutagenesis. Genetics 132, 737–753
    OpenUrlAbstract/FREE Full Text
    1. Kunapuli P.,
    2. Gurevich V. V.,
    3. Benovic J. L.
    (1994) Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5. J. Biol. Chem 269, 10209–10212
    OpenUrlAbstract/FREE Full Text
    1. Lane M. E.,
    2. Kalderon D.
    (1993) Genetic investigation of cAMP-dependent protein kinase function in Drosophila development. Genes Dev 7, 1229–43
    OpenUrlAbstract/FREE Full Text
    1. Lepage T.,
    2. Cohen S. M.,
    3. Diazbenjumea F. J.,
    4. Parkhurst S. M.
    (1995) Signal transduction by cAMP-dependent protein kinase a in Drosophila limb patterning. Nature 373, 711–715
    OpenUrlCrossRefPubMedWeb of Science
    1. Li X. J.,
    2. Wolfgang W.,
    3. Wu Y. N.,
    4. North R. A.,
    5. Forte M.
    (1991) Cloning, heterologous expression and developmental regulation of a Drosophila receptor for tachykinin-like peptides. EMBO J 10, 3221–3229
    OpenUrlPubMedWeb of Science
    1. Li X. J.,
    2. Wu Y. N.,
    3. North R. A.,
    4. Forte M.
    (1992) Cloning, functional expression, and developmental regulation of a neuropeptide Y receptor from Drosophila melanogaster. J. Biol. Chem 267, 9–12
    OpenUrlAbstract/FREE Full Text
    1. Li W.,
    2. Ohlmeyer J. T.,
    3. Lane M. E.,
    4. Kalderon D.
    (1995) Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Cell 80, 553–562
    OpenUrlCrossRefPubMedWeb of Science
    1. Luttrell L. M.,
    2. Vanbiesen T.,
    3. Hawes B. E.,
    4. Koch W. J.,
    5. Touhara K.,
    6. Lefkowitz R. J.
    (1995) G(beta-gamma) subunits mediate mitogen-activated protein kinase activation by the tyrosine kinase insulin-like growth factor 1 receptor. J. Biol. Chem 270, 16495–16498
    OpenUrlAbstract/FREE Full Text
    1. Maniatis T.,
    2. Hardison R. C.,
    3. Lacy E.,
    4. Lauer J.,
    5. O'Connell C.,
    6. Quon D.,
    7. Sim G. K.,
    8. Efstratiadis A.
    (1978) The isolation of structural genes from libraries of eucaryotic DNA. Cell 25, 687–701
    1. Margolis J.,
    2. Spradling A. C.
    (1995) Identification and behavior of epithelial stem cells in the Drosophila ovary. Development 121, 3797–3807
    OpenUrlAbstract
    1. Menard L.,
    2. Ferguson S. S. G.,
    3. Barak L. S.,
    4. Bertrand L.,
    5. Premont R. T.,
    6. Colapietro A.-M.,
    7. Lefkowitz R. J.,
    8. Caron M. G.
    (1996) Members of the G protein-coupled receptor kinase family that phosphorylate the2-adrenergic receptor facilitate sequestration. Biochem 35, 4155–4160
    OpenUrlCrossRefPubMed
    1. Monnier D.,
    2. Colas J. F.,
    3. Rosay P.,
    4. Hen F.,
    5. Borrelli E.,
    6. Maroteaux L.
    (1992) NKD, a developmentally regulated tachykinin receptor in Drosophila. J. Biol. Chem 267, 1298–1302
    OpenUrlAbstract/FREE Full Text
    1. Neuman-Silberberg F. S.,
    2. Schupbach T.
    (1993) The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGFa-like protein. Cell 75, 165–174
    OpenUrlCrossRefPubMedWeb of Science
    1. Palczewski K.,
    2. McDowell J. H.,
    3. Hargrave P. A.
    (1988) Purification and characterization of rhodopsin kinase. J. Biol. Chem 263, 14067–73
    OpenUrlAbstract/FREE Full Text
    1. Pan D. J.,
    2. Rubin G. M.
    (1995) cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. Cell 80, 543–552
    OpenUrlCrossRefPubMedWeb of Science
    1. Parks S.,
    2. Wieschaus E.
    (1991) The Drosophila gastrulation gene concertina encodes a G-like protein. Cell 64, 447–458
    OpenUrlCrossRefPubMedWeb of Science
    1. Patel N. H.,
    2. Martin-Blanco E.,
    3. Coleman K. G.,
    4. Poole S. J.,
    5. Ellis M. C.,
    6. Kornberg T. B.,
    7. Goodman C. S.
    (1989) Expression of engrailed proteins in arthropods, annelids, and chordates. Cell 58, 955–968
    OpenUrlCrossRefPubMedWeb of Science
    1. Perrimon N.
    (1994) The genetic basis of baldness in Drosophila. Cell 6, 781–784
    1. Postma R. R.,
    2. Jalink K.,
    3. Hengeveld T.,
    4. Moolenaar W. H.
    (1996) Sphingosine-1-phosphate rapidly induces Rho-dependent neurite retraction: action through a specific cell surface receptor. EMBO J 15, 2388–2395
    OpenUrlPubMedWeb of Science
    1. Premont R. T.,
    2. Inglese J.,
    3. Lefkowitz R. J.
    (1995) Protein kinases that phosphorylate activated G protein coupled receptors. FASEB J 9, 175–182
    OpenUrlAbstract
    1. Raftery L. A.,
    2. Sanicola M.,
    3. Blackman R. K.,
    4. Gelbart W. M.
    (1991) The relationship of decapentaplegic and engrailed expression in Drosophila imaginal disks: Do these genes mark the anterior-posterior compartment boundary?. Development 113, 27–33
    OpenUrlAbstract
    1. Ray Schupbach T.
    (1996) Intercellular signaling and the polarization of body axes during Drosophila oogenesis. Genes Dev 10, 14–.
    1. Sa G.,
    2. Fox P. L.
    (1994) Basic fibroblast growth factor-stimulated endothelial cell movement is mediated by a pertussis toxin-sensitive pathway regulating phospholipase A2activity. J. Biol. Chem 269, 3219–3225
    OpenUrlAbstract/FREE Full Text
    1. Saudou F.,
    2. Boschert U.,
    3. Amlaiky N.,
    4. Plassat J.-L.,
    5. Hen R.
    (1992) A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J 11, 7–17
    OpenUrlPubMedWeb of Science
    1. Shapiro R. A.,
    2. Wakimoto B. T.,
    3. Subers E. M.,
    4. Nathanson N. M.
    (1989) Characterization and functional expression in mammalian cells of genomic and cDNA clones encoding a Drosophila muscarinic acetylcholine receptor. Proc. Natl. Acad. Sci. USA 86, 9039–9043
    OpenUrlAbstract/FREE Full Text
    1. Strauss R.,
    2. Heisenberg M.
    (1993) A higher control center of locomotor behavior in the Drosophila brain. J. Neurosci 13, 1852–1861
    OpenUrlAbstract
    1. Stroumbakis N. D.,
    2. Li Z.,
    3. Tolias P. P.
    (1994) RNA-and single-stranded DNA-binding (SSB) proteins expressed during Drosophila melanogaster oogenesis: A homolog of bacterial and eukaryotic mitochondrial SSBs. Gene 143, 171–177
    OpenUrlCrossRefPubMedWeb of Science
    1. Strutt D. I.,
    2. Wiersdorff V.,
    3. Mlodzik M.
    (1995) Regulation of furrow progression in the Drosophila eye by cAMP-dependent protein kinase A. Nature 373, 705–709
    OpenUrlCrossRefPubMed
    1. Taylor S. S.,
    2. Knighton D. R.,
    3. Zheng J.,
    4. Sowadski J. M.,
    5. Gibbs C. S.,
    6. Zoller M. J.
    (1993) A template for the protein kinase family. Trends Biochem. Sci 18, 84–89
    OpenUrlCrossRefPubMedWeb of Science
    1. Twombly V.,
    2. Blackman R. K.,
    3. Jin H.,
    4. Graff J. M.,
    5. Padgett R. W.,
    6. Gelbart W. M.
    (1996) The TGF-signaling pathway is essential for Drosophila oogenesis. Development 122, 1555–1565
    OpenUrlAbstract
    1. van Biesen T.,
    2. Hawes B. E.,
    3. Raymond J. R.,
    4. Luttrell L. M.,
    5. Koch W. J.,
    6. Lefkowitz R. J.
    (1996) G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism. J. Biol. Chem 271, 1266–1269
    OpenUrlAbstract/FREE Full Text
    1. van den Heuvel M.,
    2. Ingham P. W.
    (1996) smoothened encodes a receptor-like serpentine protein required for hedgehog signaling. Nature 382, 547–551
    OpenUrlCrossRefPubMedWeb of Science
    1. Wilden U.,
    2. Hall S. W.,
    3. Kuhn H.
    (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. Proc. Natl. Acad. Sci. USA 83, 1174–8
    OpenUrlAbstract/FREE Full Text
    1. Yu S. S.,
    2. Lefkowitz R. J.,
    3. Hausdorff W. P.
    (1993) Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization. J. Biol. Chem 268, 337–41
    OpenUrlAbstract/FREE Full Text
    1. Yue L.,
    2. Spradling A. C.
    (1992) hu-li tai shao, a gene required for ring canal formation during Drosophila oogenesis, encodes a homolog of adducin. Genes Dev 6, 2443–2454
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The Drosophila G-protein-coupled receptor kinase homologue Gprk2 is required for egg morphogenesis
L.E. Schneider, A.C. Spradling
Development 1997 124: 2591-2602;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Interviews — Bénédicte Sanson and Kate Storey

Bénédicte Sanson and Kate Storey

Hear from Bénédicte Sanson, winner of the BSDB’s Cheryll Tickle medal, and Kate Storey, winner of the BSDB’s Waddington Medal, as they discuss their research, the future of the field and the importance of collaboration.

Review Commons launches

We're excited to be an affiliate journal for Review Commons, the ASAPbio/EMBO platform for high-quality journal-independent peer-review in the life sciences, which went live on 09 December.

Early-career researchers can apply for up to £2,500 to offset the cost of travel and expenses to make collaborative visits to other labs around the world. Read about Peter’s experience in Switzerland, where he joined forces with the Lutolf lab to refine a protocol for producing gastruloids.

Publishing peer review reports

To continue working towards transparency around the editorial process, Development now publishes a ‘Peer review history file’ alongside published papers. Read more about the policy and see the reports for yourself in one the first papers to publish the reports (under the ‘Info & metrics’ tab).

Development at a glance — Cell interactions in collective cell migration

Extract from the poster showing specific cell-cell interactions in metastasis.

Take a look at the latest poster and accompanying article by Denise Montell and her colleagues from the University of California, where they describe a sampling of both known and new cells that migrate collectively in vivo.