A variant form of the type C atrial natriuretic peptide receptor generated by alternative RNA splicing

A novel form of type C atrial natriuretic peptide receptor (ANP-C) was identified, characterized, and shown to be a product of alternative RNA splicing. Sequencing of several clones of ANP-C cDNA isolated from a bovine lung cDNA library revealed the presence of a new clone encoding a 536-amino acid ANP-C. The nucleotide sequence of this novel clone is very similar to that of the previously cloned ANP-C which consists of 537 amino acids. The sole difference between the two clones is the presence or absence of a very short segment of only 3 base pairs (bp), by which the sequence Ser472-Gly473 of the longer form is changed to Cys472 in the variant form; the other regions are identical. Alignment of the cDNA sequences with that of the ANP-C gene indicated that the two forms of ANP-C receptor arise from a single gene by alternative splicing using one donor and two closely located acceptor sites. Biochemical and pharmacological characterization using a mammalian cDNA expression system indicated that the two variants are similar in their subunit structures, in ligand-binding properties, and even in internalization kinetics. Polymerase chain reaction amplification of the transcripts demonstrated that 1) although the novel form is a minor species, it is present in various tissues such as the lung, kidney, adrenal, and vascular smooth muscle and endothelial cells and 2) the ratio of the novel variant form to the original longer form remains almost constant in these tissues. The alternative splicing reported here contributes to the diversity of ANP receptors; however, its physiological significance remains to be clarified.