Abstract
To begin unraveling the functional significance of calcium channel diversity, we identified mutations in Dmca1D, a Drosophila calcium channel alpha1 subunit cDNA that we recently cloned. These mutations constitute the l(2)35Fa lethal locus, which we rename Dmca1D. A severe allele, Dmca1D(X10), truncates the channel after the IV-S4 transmembrane domain. These mutants die as late embryos because they lack vigorous hatching movements. In the weaker allele, Dmca1D(AR66), a cysteine in transmembrane domain I-S1 is changed to tyrosine. Dmca1D(AR66) embryos hatch but pharate adults have difficulty eclosing. Those that do eclose have difficulty in fluid-filling of the wings. These studies show that this member of the calcium channel alpha1 subunit gene family plays a nonredundant, vital role in larvae and adults.
Full Text
The Full Text of this article is available as a PDF (563.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alphey L., Jimenez J., White-Cooper H., Dawson I., Nurse P., Glover D. M. twine, a cdc25 homolog that functions in the male and female germline of Drosophila. Cell. 1992 Jun 12;69(6):977–988. doi: 10.1016/0092-8674(92)90616-k. [DOI] [PubMed] [Google Scholar]
- Ashburner M., Thompson P., Roote J., Lasko P. F., Grau Y., el Messal M., Roth S., Simpson P. The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci. Genetics. 1990 Nov;126(3):679–694. doi: 10.1093/genetics/126.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Babitch J. Channel hands. Nature. 1990 Jul 26;346(6282):321–322. doi: 10.1038/346321b0. [DOI] [PubMed] [Google Scholar]
- Bean B. P. Classes of calcium channels in vertebrate cells. Annu Rev Physiol. 1989;51:367–384. doi: 10.1146/annurev.ph.51.030189.002055. [DOI] [PubMed] [Google Scholar]
- Blochlinger K., Bodmer R., Jan L. Y., Jan Y. N. Patterns of expression of cut, a protein required for external sensory organ development in wild-type and cut mutant Drosophila embryos. Genes Dev. 1990 Aug;4(8):1322–1331. doi: 10.1101/gad.4.8.1322. [DOI] [PubMed] [Google Scholar]
- Catterall W. A., Striessnig J. Receptor sites for Ca2+ channel antagonists. Trends Pharmacol Sci. 1992 Jun;13(6):256–262. doi: 10.1016/0165-6147(92)90079-l. [DOI] [PubMed] [Google Scholar]
- Catterall W. A. Structure and function of voltage-gated ion channels. Annu Rev Biochem. 1995;64:493–531. doi: 10.1146/annurev.bi.64.070195.002425. [DOI] [PubMed] [Google Scholar]
- Chaudhari N. A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. J Biol Chem. 1992 Dec 25;267(36):25636–25639. [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Dunlap K., Luebke J. I., Turner T. J. Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci. 1995 Feb;18(2):89–98. [PubMed] [Google Scholar]
- Fletcher C. F., Lutz C. M., O'Sullivan T. N., Shaughnessy J. D., Jr, Hawkes R., Frankel W. N., Copeland N. G., Jenkins N. A. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell. 1996 Nov 15;87(4):607–617. doi: 10.1016/s0092-8674(00)81381-1. [DOI] [PubMed] [Google Scholar]
- Fujita S. C., Zipursky S. L., Benzer S., Ferrús A., Shotwell S. L. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. doi: 10.1073/pnas.79.24.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gielow M. L., Gu G. G., Singh S. Resolution and pharmacological analysis of the voltage-dependent calcium channels of Drosophila larval muscles. J Neurosci. 1995 Sep;15(9):6085–6093. doi: 10.1523/JNEUROSCI.15-09-06085.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grabner M., Wang Z., Hering S., Striessnig J., Glossmann H. Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels. Neuron. 1996 Jan;16(1):207–218. doi: 10.1016/s0896-6273(00)80037-9. [DOI] [PubMed] [Google Scholar]
- Gu G. G., Singh S. Pharmacological analysis of heartbeat in Drosophila. J Neurobiol. 1995 Nov;28(3):269–280. doi: 10.1002/neu.480280302. [DOI] [PubMed] [Google Scholar]
- Hofmann F., Biel M., Flockerzi V. Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci. 1994;17:399–418. doi: 10.1146/annurev.ne.17.030194.002151. [DOI] [PubMed] [Google Scholar]
- Hui A., Ellinor P. T., Krizanova O., Wang J. J., Diebold R. J., Schwartz A. Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha 1 subunit of the voltage-dependent calcium channel. Neuron. 1991 Jul;7(1):35–44. doi: 10.1016/0896-6273(91)90072-8. [DOI] [PubMed] [Google Scholar]
- Ophoff R. A., Terwindt G. M., Vergouwe M. N., van Eijk R., Oefner P. J., Hoffman S. M., Lamerdin J. E., Mohrenweiser H. W., Bulman D. E., Ferrari M. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996 Nov 1;87(3):543–552. doi: 10.1016/s0092-8674(00)81373-2. [DOI] [PubMed] [Google Scholar]
- Peixoto A. A., Smith L. A., Hall J. C. Genomic organization and evolution of alternative exons in a Drosophila calcium channel gene. Genetics. 1997 Apr;145(4):1003–1013. doi: 10.1093/genetics/145.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pelzer S., Barhanin J., Pauron D., Trautwein W., Lazdunski M., Pelzer D. Diversity and novel pharmacological properties of Ca2+ channels in Drosophila brain membranes. EMBO J. 1989 Aug;8(8):2365–2371. doi: 10.1002/j.1460-2075.1989.tb08365.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perrimon N., Engstrom L., Mahowald A. P. The effects of zygotic lethal mutations on female germ-line functions in Drosophila. Dev Biol. 1984 Oct;105(2):404–414. doi: 10.1016/0012-1606(84)90297-5. [DOI] [PubMed] [Google Scholar]
- Ptácek L. J., Tawil R., Griggs R. C., Engel A. G., Layzer R. B., Kwieciński H., McManis P. G., Santiago L., Moore M., Fouad G. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell. 1994 Jun 17;77(6):863–868. doi: 10.1016/0092-8674(94)90135-x. [DOI] [PubMed] [Google Scholar]
- Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schafer W. R., Kenyon C. J. A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans. Nature. 1995 May 4;375(6526):73–78. doi: 10.1038/375073a0. [DOI] [PubMed] [Google Scholar]
- Seeger M., Tear G., Ferres-Marco D., Goodman C. S. Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron. 1993 Mar;10(3):409–426. doi: 10.1016/0896-6273(93)90330-t. [DOI] [PubMed] [Google Scholar]
- Smith L. A., Wang X., Peixoto A. A., Neumann E. K., Hall L. M., Hall J. C. A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci. 1996 Dec 15;16(24):7868–7879. doi: 10.1523/JNEUROSCI.16-24-07868.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snutch T. P., Leonard J. P., Gilbert M. M., Lester H. A., Davidson N. Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci U S A. 1990 May;87(9):3391–3395. doi: 10.1073/pnas.87.9.3391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snutch T. P., Reiner P. B. Ca2+ channels: diversity of form and function. Curr Opin Neurobiol. 1992 Jun;2(3):247–253. doi: 10.1016/0959-4388(92)90111-w. [DOI] [PubMed] [Google Scholar]
- Snutch T. P., Tomlinson W. J., Leonard J. P., Gilbert M. M. Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron. 1991 Jul;7(1):45–57. doi: 10.1016/0896-6273(91)90073-9. [DOI] [PubMed] [Google Scholar]
- Striessnig J., Glossmann H., Catterall W. A. Identification of a phenylalkylamine binding region within the alpha 1 subunit of skeletal muscle Ca2+ channels. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9108–9112. doi: 10.1073/pnas.87.23.9108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsien R. W., Ellinor P. T., Horne W. A. Molecular diversity of voltage-dependent Ca2+ channels. Trends Pharmacol Sci. 1991 Sep;12(9):349–354. doi: 10.1016/0165-6147(91)90595-j. [DOI] [PubMed] [Google Scholar]
- Vactor D. V., Sink H., Fambrough D., Tsoo R., Goodman C. S. Genes that control neuromuscular specificity in Drosophila. Cell. 1993 Jun 18;73(6):1137–1153. doi: 10.1016/0092-8674(93)90643-5. [DOI] [PubMed] [Google Scholar]
- Wei X. Y., Perez-Reyes E., Lacerda A. E., Schuster G., Brown A. M., Birnbaumer L. Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels. J Biol Chem. 1991 Nov 15;266(32):21943–21947. [PubMed] [Google Scholar]
- de Leon M., Wang Y., Jones L., Perez-Reyes E., Wei X., Soong T. W., Snutch T. P., Yue D. T. Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type Ca2+ channels. Science. 1995 Dec 1;270(5241):1502–1506. doi: 10.1126/science.270.5241.1502. [DOI] [PubMed] [Google Scholar]