ROLE OF CARBOXYL TAIL OF THE RAT ANGIOTENSIN-II TYPE 1A RECEPTOR IN AGONIST-INDUCED INTERNALIZATION OF THE RECEPTOR

Role of carboxyl tail of the rat angiotensin II type 1A receptor in agonist-induced internalization of the receptor. Binding of angiotensin II (Ang II) to its receptor type 1A (AT(1A)) is known to trigger its internalization. We studied the role of cytosolic segments of AT(1A) in the internalization, and obtained results indicating a functional role of the cytosolic carboxyl terminal tail of AT(1A) in the internalization. Deletion of 50 amino acids from the carboxyl terminus abolished the receptor internalization. Deletion mutants lacking 13 and 32 amino acid residues in the carboxyl terminal cytosolic region were internalized to the same extent as wild type AT(1A); however, internalization of a mutant lacking the last 42 residues was partially suppressed. Thus, residues 310 through 327 were shown to be essential for the internalization. We propose that a short domain in the cytoplasmic tail (residues 310 to 327) may play a dominant role in the agonist-induced receptor internalization of AT(1A). Our results also suggest that the molecular determinants of the AT(1A) receptor involved in receptor internalization are distinct from those participating in the desensitization process. IMPORTANT: Please read the Note Added in Proof at the end of the article (p. 1495) for important information!