Two Drosophila Genes That Encode the and Subunits of the Brain Soluble Guanylyl Cyclase (*)

Abstract

We identified two Drosophila genes (dgcα1 and dgcβ1) that encode the soluble guanylyl cyclase α and β subunits, respectively. The putative Dgcα1 protein is 76 kDa, has 35% amino acid identity with previously isolated α subunits, and was immunolocalized to the adult retina, to the optic lobes, and throughout the brain neuropil. The Dgcβ1 protein is 86 kDa and exhibits 59% amino acid identity with the rat β1 protein. However, the Dgcβ1 protein has an additional 118 amino acids inserted near the amino terminus, which makes it significantly larger than the rat β1. The Dgcβ1 protein was immunolocalized to the optic lobes and throughout the brain neuropil, with no detectable expression in the retina. The Dgcα1 and Dgcβ1 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 Dgcα1 and Dgcβ1 are soluble guanylyl cyclase α and β subunits that are capable of forming a functional guanylyl cyclase heterodimer.