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J. Biol. Chem., Vol. 279, Issue 49, 50651-50653, December 3, 2004

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Atypical Soluble Guanylyl Cyclases in Drosophila Can Function as Molecular Oxygen Sensors^*

David B. Morton

From the Department of Integrative Biosciences, Oregon Health & Science University, Portland, Oregon 97239

Conventional soluble guanylyl cyclases are heterodimeric enzymes that synthesize cGMP and are activated by nitric oxide. Recently, a separate class of soluble guanylyl cyclases has been identified that are only slightly activated by or are insensitive to nitric oxide. These atypical guanylyl cyclases include the vertebrate 2 subunit and examples from the invertebrates Manduca sexta, Caenorhabditis elegans, and Drosophila melanogaster. A member of this family, GCY-35 in C. elegans, was recently shown to be required for a behavioral response to low oxygen levels and may be directly regulated by oxygen (Gray, J. M., Karow, D. S., Lu, H., Chang, A. J., Chang, J. S., Ellis, R. E., Marletta, M. A., and Bargmann, C. I. (2004) Nature 430, 317–322). Drosophila contains three genes that code for atypical soluble guanylyl cyclases: Gyc-88E, Gyc-89Da, and Gyc-89Db. COS-7 cells co-transfected with Gyc-88E and Gyc-89Da or Gyc-89Db accumulate low levels of cGMP under normal atmospheric oxygen concentrations and are potently activated under anoxic conditions. The increase in activity is graded over oxygen concentrations of 0–21%, can be detected within 1 min of exposure to anoxic conditions and is blocked by the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). Gyc-88E and Gyc-89Db are co-expressed in a subset of sensory neurons where they would be ideally situated to act as oxygen sensors. This is the first demonstration of a soluble guanylyl cyclase that is activated in response to changing oxygen concentrations.

Received for publication, September 29, 2004

^* This work was supported by National Institutes of Health Grant NS29740. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Integrative Biosciences, SD, 611 SW Campus Dr., Oregon Health & Science University, Portland, OR 97239. Tel.: 503-494-8596; Fax: 503-494-8554; E-mail: mortonda{at}ohsu.edu.

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This article has been cited by other articles:

				D. B. Morton, J. A. Stewart, K. K. Langlais, R. A. Clemens-Grisham, and A. Vermehren Synaptic transmission in neurons that express the Drosophila atypical soluble guanylyl cyclases, Gyc-89Da and Gyc-89Db, is necessary for the successful completion of larval and adult ecdysis J. Exp. Biol., May 15, 2008; 211(10): 1645 - 1656. [Abstract] [Full Text] [PDF]

				A. R. Mendenhall, B. LaRue, and P. A. Padilla Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans Genetics, November 1, 2006; 174(3): 1173 - 1187. [Abstract] [Full Text] [PDF]

				A. Woods INSECT MOLECULAR OXYGEN SENSOR FOUND J. Exp. Biol., April 1, 2005; 208(7): v - v. [Full Text] [PDF]