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Calbindin‐D 28K dynamically controls TRPV5‐mediated Ca 2+ transport
Author(s) -
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
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601186
Subject(s) - transcellular , cytosol , biology , extracellular , calbindin , paracellular transport , biophysics , transport protein , calcium , microbiology and biotechnology , orai1 , biochemistry , endoplasmic reticulum , membrane , chemistry , stim1 , permeability (electromagnetism) , immunology , organic chemistry , enzyme , immunohistochemistry
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.

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