Membrane Trafficking of Angiotensin Receptor Type-1 and Mechanochemical Signal Transduction in Proximal Tubule Cells

Abstract

Cellular localization and trafficking of the major angiotensin receptor, AT 1 , was studied in mouse proximal tubule cell lines because angiotensin II concentrations in the luminal fluid of proximal tubules are greater than the K d of the receptor and would predict high turnover rates of the receptor. Mouse proximal tubule cells can exist in 2 polarized, differentiated states after confluence: a protoepithelium and a highly differentiated epithelium. The latter is distinguished by greater polarization of the microtubule cytoskeleton and collection of apical microtubule-dependent membrane proteins in condensed apical recycling endosomes (CARE) in proximity to the primary cilium. AT 1 , AT 2 , and the sodium hydrogen exchanger NHE3 are localized to CARE. With fluid movement, AT 1 receptors externalize from CARE to the apical plasma membrane and allow luminal angiotensin II to initiate cell signaling. These data suggest that fluid movement controls receptor externalization and, hence, a model in which ciliary deflection results in transduction of a mechanical stimulus into the chemical signaling of the AT 1 receptor.