Identification of a novel guanylyl cyclase that is related to receptor guanylyl cyclases, but lacks extracellular and transmembrane domains

We have identified a novel guanylyl cyclase, named MsGC-I, that is expresse d in the nervous system of Manduca sexta. MsGC-I shows highest sequence ide ntity with receptor guanylyl cyclases throughout its catalytic and dimeriza tion domains but does not contain the ligand-binding, transmembrane, or kin ase-like domains characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C-terminal extension of 149 amino acids that is not pres ent in other receptor guanylyl cyclases; The sequence of MsGC-I contains no regions that show similarity to the regulatory domain of soluble guanylyl cyclases, Thus, MsGC-I appears to represent a member of a new class of guan ylyl cyclases, We show that both a transcript and a protein of the sizes pr edicted from the MsGC-I cDNA are present in the nervous system of Manduca a nd that MsGC-I is expressed in a small population of neurons within the abd ominal ganglia, When expressed in COS-7 cells, MsGC-I appears to exist as a soluble homodimer with high levels of basal guanylyl cyclase activity that is insensitive to stimulation by nitric oxide. Western blot analysis, howe ver, shows that MsGC-I is localized to the particulate fraction of nervous system homogenates, suggesting that it may be membrane-associated in vivo.