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  • The EMBO Journal (2006) 25, 2978 - 2988
  • doi:10.1038/sj.emboj.7601186

Published online: 8 June 2006

Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport

Tim T Lambers1, Frank Mahieu3, Elena Oancea4, Louis Hoofd1, Frank de Lange2, Arjen R Mensenkamp1, Thomas Voets3, Bernd Nilius3, David E Clapham3,4, Joost G Hoenderop1 and René J Bindels1

  1. Department of Physiology, Radboud University Nijmegen Medical Centre, The Netherlands
  2. Department of Cell Biology, Radboud University Nijmegen Medical Centre, The Netherlands
  3. Department of Physiology, KU Leuven, Campus Gasthuisberg, Leuven, Belgium
  4. Cardiovascular Department, HHMI, Children's Hospital and Department of Neurobiology, Harvard Medical School, USA

Correspondence to:

René J Bindels, Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 24 3614211; Fax: +31 24 3616413; E-mail: R.Bindels@ncmls.ru.nl

Received 27 January 2006; Accepted 16 May 2006

In Ca2+-transporting epithelia, calbindin-D28K (CaBP28K) facilitates Ca2+ diffusion from the luminal Ca2+ entry side of the cell to the basolateral side, where Ca2+ is extruded into the extracellular compartment. Simultaneously, CaBP28K provides protection against toxic high Ca2+ levels by buffering the cytosolic Ca2+ concentration ([Ca2+]i) during high Ca2+ influx. CaBP28K consistently colocalizes with the epithelial Ca2+ channel TRPV5, which constitutes the apical entry step in renal Ca2+-transporting epithelial cells. Here, we demonstrate using protein-binding analysis, subcellular fractionation and evanescent-field microscopy that CaBP28K translocates towards the plasma membrane and directly associates with TRPV5 at a low [Ca2+]i. 45Ca2+ uptake measurements, electrophysiological recordings and transcellular Ca2+ transport assays of lentivirus-infected primary rabbit connecting tubule/distal convolute tubule cells revealed that associated CaBP28K tightly buffers the flux of Ca2+ entering the cell via TRPV5, facilitating high Ca2+ transport rates by preventing channel inactivation. In summary, CaBP28K acts in Ca2+-transporting epithelia as a dynamic Ca2+ buffer, regulating [Ca2+] in close vicinity to the TRPV5 pore by direct association with the channel.

  • Keywords:

    • Ca2+ homeostasis,
    • kidney,
    • TIRF,
    • transient receptor potential,
    • vitamin D