TRPV5 is internalized via clathrin-dependent endocytosis to enter a Ca2+-controlled recycling pathway |
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Authors: | van de Graaf Stan F J Rescher Ursula Hoenderop Joost G J Verkaart Sjoerd Bindels René J M Gerke Volker |
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Institution: | Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, von-Esmarch-Strasse 56, Münster 48149, Germany. S.VandeGraaf-4@umcutrecht.nl |
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Abstract: | The epithelial Ca(2+) channel TRPV5 plays an essential role in transcellular Ca(2+) transport and is one of the most Ca(2+)-selective members of the transient receptor potential superfamily. Regulation of the abundance of TRPV5 at the cell surface is critical in body Ca(2+) homeostasis. However, little is known about the mechanisms underlying TRPV5 endo- and exocytosis. Here, we show that TRPV5 is constitutively internalized in a dynamin- and clathrin-dependent manner. Internalized TRPV5 first appears in small vesicular structures and then localizes to perinuclear structures positive for Rab11a. TRPV5 has a half-life of more than 8 h and is stable even after internalization from the cell surface for more than 3 h. Disruption of cell surface delivery of newly synthesized TRPV5 by brefeldin A does not reduce TRPV5-mediated Ca(2+) influx in cells, suggesting the presence of a stable intracellular pool of the channel capable of recycling back to the surface. Furthermore, the endocytic recycling kinetics is decreased upon treatment with Ca(2+) chelator BAPTA-AM, indicating that the channel's trafficking pathways are dynamically controlled by Ca(2+). |
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