Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport

EMBO J. 2006 Jul 12;25(13):2978-88. doi: 10.1038/sj.emboj.7601186. Epub 2006 Jun 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 1
  • Calbindins
  • Calcium / physiology*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Dogs
  • Epithelial Cells / metabolism
  • Humans
  • Ion Transport
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Protein Binding
  • Protein Transport
  • Rabbits
  • Recombinant Proteins / metabolism
  • S100 Calcium Binding Protein G / physiology*
  • TRPV Cation Channels / physiology*
  • Urothelium / cytology
  • Urothelium / metabolism


  • CALB1 protein, human
  • Calbindin 1
  • Calbindins
  • Recombinant Proteins
  • S100 Calcium Binding Protein G
  • TRPV Cation Channels
  • Calcium