Molecular cloning of a retina-specific membrane guanylyl cyclase.
We have isolated and characterized cDNA clones encoding the human retinal guanylyl cyclase (retGC), a novel member of the membrane guanylyl cyclase gene family. Like other membrane guanylyl cyclases, the 1101 aa retGC is predicted to have a hydrophobic amino-terminal signal sequence followed by a large extracellular domain, a single membrane spanning domain, a kinase homology domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane guanylyl cyclases, such as natriuretic peptide receptors, retGC has a relatively high basal level of activity when expressed in human 293 cells. cGMP production by retGC is unaffected by any of the known natriuretic peptides. In situ hybridization analysis of a variety of rhesus monkey tissues showed retGC transcripts to be localized exclusively along the retinal outer nuclear layer, corresponding to the nuclei of the rod and cone photoreceptor cells. Our results suggest that retGC may synthesize cGMP required for recovery of the dark state after phototransduction.
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
A W
AW
Shyjan
F J
FJ
de Sauvage
N A
NA
Gillett
D V
DV
Goeddel
D G
DG
Lowe
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012160:Retina / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D006162:Guanylate Cyclase