Abstract
Using a strategy based on nucleotide sequence homology between genes encoding receptors that interact with guanine nucleotide-binding proteins, we have isolated Drosophila genomic and cDNA clones encoding a functional serotonin receptor (5HT-dro receptor). This protein is expressed predominantly in Drosophila heads and exhibits highest homology with the human 5HT1A receptor. The predicted structure of the 5HT-dro receptor reveals two unusual features: (i) eight putative transmembrane domains instead of the expected seven and (ii) a Gly-Ser repeat that is a potential glycosaminoglycan attachment site. When stably introduced into mouse NIH 3T3 cells, the 5HT-dro receptor activates adenylate cyclase in response to serotonin and is inhibited by serotonin receptor antagonists such as dihydroergocryptine. The 5HT-dro receptor or closely related receptors might be responsible for the serotonin-sensitive cyclase that has been suggested to play a role in learning and modulation of circadian rhythm in a number of invertebrate systems.
Full text
PDF![8940](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9674/55076/30f89645b94a/pnas01047-0263.png)
![8941](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9674/55076/6246fbd9a620/pnas01047-0264.png)
![8942](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9674/55076/8381251ce00a/pnas01047-0265.png)
![8943](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9674/55076/e055037dffab/pnas01047-0266.png)
![8944](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9674/55076/9a5551eb56db/pnas01047-0267.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arakawa S., Gocayne J. D., McCombie W. R., Urquhart D. A., Hall L. M., Fraser C. M., Venter J. C. Cloning, localization, and permanent expression of a Drosophila octopamine receptor. Neuron. 1990 Mar;4(3):343–354. doi: 10.1016/0896-6273(90)90047-j. [DOI] [PubMed] [Google Scholar]
- Bargiello T. A., Young M. W. Molecular genetics of a biological clock in Drosophila. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2142–2146. doi: 10.1073/pnas.81.7.2142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J., Heslop J. P. Separate 5-hydroxytryptamine receptors on the salivary gland of the blowfly are linked to the generation of either cyclic adenosine 3',5'-monophosphate or calcium signals. Br J Pharmacol. 1981 Jul;73(3):729–738. doi: 10.1111/j.1476-5381.1981.tb16809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bourdon M. A., Oldberg A., Pierschbacher M., Ruoslahti E. Molecular cloning and sequence analysis of a chondroitin sulfate proteoglycan cDNA. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1321–1325. doi: 10.1073/pnas.82.5.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bunzow J. R., Van Tol H. H., Grandy D. K., Albert P., Salon J., Christie M., Machida C. A., Neve K. A., Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988 Dec 22;336(6201):783–787. doi: 10.1038/336783a0. [DOI] [PubMed] [Google Scholar]
- Dixon R. A., Kobilka B. K., Strader D. J., Benovic J. L., Dohlman H. G., Frielle T., Bolanowski M. A., Bennett C. D., Rands E., Diehl R. E. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature. 1986 May 1;321(6065):75–79. doi: 10.1038/321075a0. [DOI] [PubMed] [Google Scholar]
- Dudai Y. Neurogenetic dissection of learning and short-term memory in Drosophila. Annu Rev Neurosci. 1988;11:537–563. doi: 10.1146/annurev.ne.11.030188.002541. [DOI] [PubMed] [Google Scholar]
- Dudai Y., Zvi S. Aminergic receptors in Drosophila melanogaster: properties of [3H]dihydroergocryptine binding sites. J Neurochem. 1982 Jun;38(6):1551–1558. doi: 10.1111/j.1471-4159.1982.tb06632.x. [DOI] [PubMed] [Google Scholar]
- Dudai Y., Zvi S. [3H]serotonin binds to two classes of sites in Drosophila head homogenate. Comp Biochem Physiol C. 1984;77(2):305–309. doi: 10.1016/0742-8413(84)90018-5. [DOI] [PubMed] [Google Scholar]
- Eskin A., Corrent G., Lin C. Y., McAdoo D. J. Mechanism for shifting the phase of a circadian rhythm by serotonin: involvement of cAMP. Proc Natl Acad Sci U S A. 1982 Jan;79(2):660–664. doi: 10.1073/pnas.79.2.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fargin A., Raymond J. R., Lohse M. J., Kobilka B. K., Caron M. G., Lefkowitz R. J. The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature. 1988 Sep 22;335(6188):358–360. doi: 10.1038/335358a0. [DOI] [PubMed] [Google Scholar]
- Frielle T., Collins S., Daniel K. W., Caron M. G., Lefkowitz R. J., Kobilka B. K. Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920–7924. doi: 10.1073/pnas.84.22.7920. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green S., Issemann I., Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. doi: 10.1093/nar/16.1.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Julius D., MacDermott A. B., Axel R., Jessell T. M. Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science. 1988 Jul 29;241(4865):558–564. doi: 10.1126/science.3399891. [DOI] [PubMed] [Google Scholar]
- Kadan M. J., Hartig P. R. Autoradiographic localization and characterization of [125I]lysergic acid diethylamide binding to serotonin receptors in Aplysia. Neuroscience. 1988 Mar;24(3):1089–1102. doi: 10.1016/0306-4522(88)90090-5. [DOI] [PubMed] [Google Scholar]
- Kandel E. R., Abrams T., Bernier L., Carew T. J., Hawkins R. D., Schwartz J. H. Classical conditioning and sensitization share aspects of the same molecular cascade in Aplysia. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):821–830. doi: 10.1101/sqb.1983.048.01.085. [DOI] [PubMed] [Google Scholar]
- Kobilka B. K., Matsui H., Kobilka T. S., Yang-Feng T. L., Francke U., Caron M. G., Lefkowitz R. J., Regan J. W. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650–656. doi: 10.1126/science.2823383. [DOI] [PubMed] [Google Scholar]
- Litosch I., Fradin M., Kasaian M., Lee H. S., Fain J. N. Regulation of adenylate cyclase and cyclic AMP phosphodiesterase by 5-hydroxytryptamine and calcium ions in blowfly salivary-gland homogenates. Biochem J. 1982 Apr 15;204(1):153–159. doi: 10.1042/bj2040153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McClung C. R., Fox B. A., Dunlap J. C. The Neurospora clock gene frequency shares a sequence element with the Drosophila clock gene period. Nature. 1989 Jun 15;339(6225):558–562. doi: 10.1038/339558a0. [DOI] [PubMed] [Google Scholar]
- Nathanson J. A., Greengard P. Serotonin-sensitive adenylate cyclase in neural tissue and its similarity to the serotonin receptor: a possible site of action of lysergic acid diethylamide. Proc Natl Acad Sci U S A. 1974 Mar;71(3):797–801. doi: 10.1073/pnas.71.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Dowd B. F., Lefkowitz R. J., Caron M. G. Structure of the adrenergic and related receptors. Annu Rev Neurosci. 1989;12:67–83. doi: 10.1146/annurev.ne.12.030189.000435. [DOI] [PubMed] [Google Scholar]
- Peroutka S. J. 5-Hydroxytryptamine receptor subtypes. Annu Rev Neurosci. 1988;11:45–60. doi: 10.1146/annurev.ne.11.030188.000401. [DOI] [PubMed] [Google Scholar]
- Pritchett D. B., Bach A. W., Wozny M., Taleb O., Dal Toso R., Shih J. C., Seeburg P. H. Structure and functional expression of cloned rat serotonin 5HT-2 receptor. EMBO J. 1988 Dec 20;7(13):4135–4140. doi: 10.1002/j.1460-2075.1988.tb03308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quan F., Wolfgang W. J., Forte M. A. The Drosophila gene coding for the alpha subunit of a stimulatory G protein is preferentially expressed in the nervous system. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4321–4325. doi: 10.1073/pnas.86.11.4321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddy P., Jacquier A. C., Abovich N., Petersen G., Rosbash M. The period clock locus of D. melanogaster codes for a proteoglycan. Cell. 1986 Jul 4;46(1):53–61. doi: 10.1016/0092-8674(86)90859-7. [DOI] [PubMed] [Google Scholar]
- Ruoslahti E. Structure and biology of proteoglycans. Annu Rev Cell Biol. 1988;4:229–255. doi: 10.1146/annurev.cb.04.110188.001305. [DOI] [PubMed] [Google Scholar]
- Sanes J. R. Extracellular matrix molecules that influence neural development. Annu Rev Neurosci. 1989;12:491–516. doi: 10.1146/annurev.ne.12.030189.002423. [DOI] [PubMed] [Google Scholar]
- Takahashi J. S., Zatz M. Regulation of circadian rhythmicity. Science. 1982 Sep 17;217(4565):1104–1111. doi: 10.1126/science.6287576. [DOI] [PubMed] [Google Scholar]
- Tempel B. L., Livingstone M. S., Quinn W. G. Mutations in the dopa decarboxylase gene affect learning in Drosophila. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3577–3581. doi: 10.1073/pnas.81.11.3577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uzzan A., Dudai Y. Aminergic receptors in Drosophila melanogaster: responsiveness of adenylate cyclase to putative neurotransmitters. J Neurochem. 1982 Jun;38(6):1542–1550. doi: 10.1111/j.1471-4159.1982.tb06631.x. [DOI] [PubMed] [Google Scholar]
- Zehring W. A., Wheeler D. A., Reddy P., Konopka R. J., Kyriacou C. P., Rosbash M., Hall J. C. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell. 1984 Dec;39(2 Pt 1):369–376. doi: 10.1016/0092-8674(84)90015-1. [DOI] [PubMed] [Google Scholar]