Published Online
on July 19, 2004

A more recent version of this article appeared on September 1, 2004

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Submitted on March 22, 2004
Revised on April 6, 2004

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

Robert J. Kolb; Philip G. Woost; and Ulrich Hopfer^*

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

^* To whom correspondence should be addressed. E-mail: ulrich.hopfer{at}case.edu.

Abstract--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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