2 MEMBRANE FORMS OF GUANYLYL CYCLASE FOUND IN THE EYE

The cDNAs for two membrane guanylyl cyclases, designated E (GC-E) and F (GC-F), were isolated from a rat eye cDNA library, Their deduced topographic structures correspond to known members of the guanylyl cyclase receptor family, containing an extracellular domain, a single membrane-spanning domain, a protein kinase-like domain, and a cyclase catalytic domain, GC-E was expressed in the eye and the pineal gland, whereas GC-F expression was confined to the eye, Overproduction of GC-E and GC-F in COS cells resulted in expression of guanylyl cyclase activity, but ligands known to activate other guanylyl cyclase receptors failed to stimulate enzyme activity, Thus, both GC-E and GC-F remain orphan receptors. Amino acid sequence similarity between GC-E and GC-F in the extracellular region and homology with a cyclase expressed in olfactory neurons and retGC, a rod outer-segment-specific cyclase, suggest that there is another subfamily of guanylyl cyclase receptors, possibly restricted to sensory tissues.