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(Hypertension. 2004;44:352.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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

From the Department of Physiology and Biophysics Case Western Reserve University, Cleveland, Ohio.

Correspondence to Ulrich Hopfer, Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970. E-mail ulrich.hopfer{at}case.edu

Cellular localization and trafficking of the major angiotensin receptor, AT₁, 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. AT₁, AT₂, and the sodium hydrogen exchanger NHE3 are localized to CARE. With fluid movement, AT₁ 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 AT₁ receptor.

Key Words: receptors, angiotensin • epithelium • microscopy • kidney

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