Angiotensin II‐Induced Golgi Translocation of the AT1 and AT2 Receptors

AT 1 and AT 2 receptors are G protein‐coupled seven transmembrane receptors. They bind Angiotensin II (Ang II), an octapeptide hormone, to regulate diverse physiological actions. Similar to most GPCRs, AT 1 but not AT 2 receptor expressed on the cell surface undergoes conventional endocytosis for degradation and recycling upon ligand activation. Interestingly, recent evidence shows that Ang II also induces nuclear translocation of the AT 1 receptors. In HEK293 cells that stably express AT 1 and AT 2 receptors tagged with GFP at the C‐terminal or HA at the N‐terminal (AT 1 ‐GFP, HA‐AT 2 ‐GFP, HA‐AT 1 and HA‐AT 2 ), we observed Ang II‐induced perinuclear accumulation of the AT 1 receptors under confocal laser scanning microscope. Surprisingly, Ang II also induced Golgi accumulation of both receptors as detected with Golgi‐specific dye BODPIY TR. Distinct from conventional endocytosis that results in about 50% AT 1 receptor internalization within the first 15 min of Ang II stimulation, the Golgi accumulation occurred 30 min after the stimulation. With fluorescein‐labeled FITC‐Ang II, we found that FITC‐Ang II co‐localizes with AT 1 and AT 2 receptors in the Golgi. DRY/tL 314 , an AT 1 mutant deficient in G protein activation and conventional internalization, underwent almost intact Golgi translocation, suggesting a novel endocytosis pathway. In conclusion, we have identified the Ang II‐induced translocation of AT 1 and AT 2 receptors from plasma membrane to Golgi. These results suggest an undefined function of Golgi in receptor endocytosis and/or an unidentified role of Ang II receptors in regulation of Golgi function. The work is supported by NHLBI HL65492 to YHF.