2 DROSOPHILA GENES THAT ENCODE THE ALPHA-SUBUNIT AND BETA-SUBUNIT OF THE BRAIN SOLUBLE GUANYLYL CYCLASE

We identified two Drosophila genes (dgc alpha 1 and dgc beta 1) that encode the soluble guanylyl cyclase alpha and beta subunits, respectively. The putative Dgc alpha 1 protein is 76 kDa, has 35% amino acid identity with previously isolated alpha subunits, and was immunolocalized to the adult retina, to the optic lobes, and throughout the brain neuropil. The Dgc beta 1 protein is 86 kDa and exhibits 59% amino acid identity with the rat beta 1 protein. However, the Dgc beta 1 protein has an additional 118 amino acids inserted near the amino terminus, which makes it significantly larger than the rat beta 1. The Dgc beta 1 protein was immunolocalized to the optic lobes and throughout the brain neuropil, with no detectable expression in the retina. The Dgc alpha 1 and Dgc beta 1 cDNAs were stably transfected into human kidney 293 cells. Expression of the individual subunits and mixing of the individually expressed subunits failed to generate significant guanylyl cyclase activity. Only coexpression of the subunits resulted in significant guanylyl cyclase activity. Our results indicate that Dgc alpha 1 and Dgc beta 1 are soluble guanylyl cyclase alpha and beta subunits that are capable of forming a functional guanylyl cyclase heterodimer.