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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2004-09, Vol.44 (3), p.352-359
• Main Authors: Kolb, Robert J, Woost, Philip G, Hopfer, Ulrich
• Format: Article
• Language: English
• Subjects: Angiotensin II - physiology; Animals; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Cell Culture Techniques - methods; Cell Differentiation - drug effects; Cell Line - drug effects; Cell Line - metabolism; Cell Line - ultrastructure; Cell Membrane - metabolism; Cell Polarity - drug effects; Cilia - metabolism; Cilia - ultrastructure; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Culture Media - pharmacology; Dogs; Endosomes - physiology; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Medical sciences; Membrane Proteins - metabolism; Mice; Microscopy, Fluorescence; Microtubules - physiology; Pharmacology. Drug treatments; Protein Transport; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - metabolism; Receptors, Mitogen - analysis; Rheology; Signal Transduction - physiology; Sodium - metabolism; Temperature
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000136645.90116.1a

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 Kd of the receptor and would predict high turnover rates of the receptor. Mouse proximal tubule cells can exist in 2 polarized, differentiated states after confluencea 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.