Identification of an orphan guanylate cyclase receptor selectively expressed in mouse testis.
We have identified a novel membrane form of guanylate cyclase (GC) from a mouse testis cDNA library and termed it mGC-G (mouse GC-G) based on its high sequence homology to rat GC-G. It encodes a potential type I transmembrane receptor, with the characteristic domain structure common to all members of the family of membrane GCs, including an extracellular, putative ligand-binding domain, a single membrane-spanning segment and cytoplasmic protein kinase-like and cyclase catalytic domains. Real-time quantitative reverse transcriptase--PCR and Northern-blot analyses showed that mGC-G is highly and selectively expressed in mouse testis. Phylogenetic analysis based on the extracellular protein sequence revealed that mGC-G is closely related to members of the subfamily of natriuretic peptide receptor GCs. When overexpressed in HEK-293T cells (human embryonic kidney 293T cells) or COS-7 cells, mGC-G manifests as a membrane-bound glycoprotein, which can form either homomeric or heteromeric complexes with the natriuretic peptide receptor GC-A. It exhibits marked cGMP-generating GC activity; however, notably, all ligands known to activate other receptor GCs failed to stimulate enzymic activity. The unique testis-enriched expression of mGC-G, which is completely different from the broader tissue distribution of rat GC-G, suggests the existence of as-yet-unidentified ligands and unappreciated species-specific physiological functions mediated through mGC-G/cGMP signalling in the testis.
Kuhn
Michaela
M
Institut fuer Pharmakologie und Toxikologie, Universitaetsklinikum Muenster, Muenster, Germany.
Ng
Chi Kin Domingos
CK
Su
Yueh-Hsing
YH
Kilić
Ana
A
Mitko
Danuta
D
Bien-Ly
Nga
N
Kömüves
László G
LG
Yang
Ruey-Bing
RB
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006162:Guanylate Cyclase / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides / Q000494:pharmacology; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D014018:Tissue Distribution
D008565:Membrane Proteins; D045265:Natriuretic Peptides; D011956:Receptors, Cell Surface; C487900:GC-G protein, mouse; D006162:Guanylate Cyclase; D006152:Cyclic GMP