Title: Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport
Authors: Lambers, Tim T ×
Mahieu, Frank
Oancea, Elena
Hoofd, Louis
de Lange, Frank
Mensenkamp, Arjen R
Voets, Thomas
Nilius, Bernd
Clapham, David E
Hoenderop, Joost G
Bindels, René J #
Issue Date: Jul-2006
Publisher: Nature Publishing Group
Series Title: EMBO Journal vol:25 issue:13 pages:2978-2988
Abstract: In Ca(2+)-transporting epithelia, calbindin-D(28K) (CaBP(28K)) facilitates Ca(2+) diffusion from the luminal Ca(2+) entry side of the cell to the basolateral side, where Ca(2+) is extruded into the extracellular compartment. Simultaneously, CaBP(28K) provides protection against toxic high Ca(2+) levels by buffering the cytosolic Ca(2+) concentration ([Ca(2+)](i)) during high Ca(2+) influx. CaBP(28K) consistently colocalizes with the epithelial Ca(2+) channel TRPV5, which constitutes the apical entry step in renal Ca(2+)-transporting epithelial cells. Here, we demonstrate using protein-binding analysis, subcellular fractionation and evanescent-field microscopy that CaBP(28K) translocates towards the plasma membrane and directly associates with TRPV5 at a low [Ca(2+)](i). (45)Ca(2+) uptake measurements, electrophysiological recordings and transcellular Ca(2+) transport assays of lentivirus-infected primary rabbit connecting tubule/distal convolute tubule cells revealed that associated CaBP(28K) tightly buffers the flux of Ca(2+) entering the cell via TRPV5, facilitating high Ca(2+) transport rates by preventing channel inactivation. In summary, CaBP(28K) acts in Ca(2+)-transporting epithelia as a dynamic Ca(2+) buffer, regulating [Ca(2+)] in close vicinity to the TRPV5 pore by direct association with the channel.
ISSN: 0261-4189
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Department of Materials Engineering - miscellaneous
Laboratory of Ion Channel Research
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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