Endocytosis and signaling of angiotensin II type 1 receptor

A vasoactive octapeptide angiotensin II (Ang II) hormone is the key regulator of the renin-angiotensin system (RAS). It binds with the two different plasma membrane receptors like angiotensin II type 1 (AT1) and type 2 (AT2) and consequence various biological responses occur. Further, AT1 has two subtypes such as AT1A and AT1B. These angiotensin receptors are classified to be G protein-coupled receptors (GPCRs). The main constituent of RAS is the AT1 receptor (AT1R), and its activation, signal transduction, and regulation have been extensively studied. After Ang II stimulation, the ligand-receptor complexes internalized and trafficked through the early endosome, recycling endosome, and some receptors skipped the recycling endosome and trafficked to the lysosome for metabolic degradation. Moreover, some short sequence motifs located in the carboxyl-terminus (CT) of the receptor play a vital role in the internalization, phosphorylation, subcellular trafficking, signaling, and desensitization. Furthermore, in endocytosis, the various proteins interact with the CT region of the receptor. This chapter highlights the basic mechanism of AT1 receptor internalization, trafficking and signaling in both physiological and pathophysiological conditions.