Ligand-independent oligomerization of natriuretic peptide receptors. Identification of heteromeric receptors and a dominant negative mutant.
Activation of many single-transmembrane receptors requires ligand-induced receptor oligomerization. We have examined the oligomerization of the atrial natriuretic peptide receptor, NPR-A, using epitope-tagged receptor in a co-immunoprecipitation assay. Unlike other single-transmembrane receptors, NPR-A oligomerized in a ligand-independent fashion. Extracellular receptor sequences were both necessary and sufficient for oligomer formation. NPR-A was also able to oligomerize with the related natriuretic peptide receptor, NPR-B. A truncated NPR-A lacking most of the cytoplasmic domain blocked activation of the full-length receptor, presumably through formation of an inactive heteromer. These results indicate that oligomerization of this single-transmembrane receptor is important for the transduction of a conformational change across the plasma membrane but are not consistent with models in which natriuretic peptide receptor oligomerization serves merely to bring intracellular domains together.
Chinkers
M
M
Vollum Institute for Advanced Biomedical Research, Portland, Oregon.
Wilson
E M
EM
D000595:Amino Acid Sequence; D009320:Atrial Natriuretic Factor / Q000737:chemistry*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D000939:Epitopes; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D011233:Precipitin Tests; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D014162:Transfection
D000939:Epitopes; D008024:Ligands; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP