Regulation of the epithelial calcium channel TRPV5 by extracellular factors.
OBJECTIVE
Recent studies have greatly increased our knowledge concerning the regulation of renal calcium handling. This review focuses on newly identified calciotropic factors present in the pro-urine and the mechanisms by which they control the transient receptor potential channel vanilloid subtype 5 (TRPV5) which forms the gatekeeper of active renal calcium reabsorption.


RESULTS
The antiaging hormone klotho regulates TRPV5 activity via a novel mechanism modifying its glycosylation status, thereby entrapping the channel at the cell surface. Functional characterization of tissue kallikrein knockout mice revealed that these animals exhibit a pronounced hypercalciuria, comparable to the calcium leak observed in TRPV5 knockout mice. Recently, it has been demonstrated that tissue kallikrein stimulates active calcium reabsorption via the bradykinin receptor type 2 pathway involving protein kinase C-dependent activation of TRPV5. Finally, the extracellular pH appears to act as a dynamic switch controlling cell surface expression of TRPV5.


CONCLUSIONS
Unraveling the molecular mechanisms of TRPV5 channel regulation by the antiaging hormone klotho, tissue kallikrein and extracellular pH demonstrated the existence of novel regulatory mechanisms of active calcium reabsorption acting from the tubular lumen.
Topala
Catalin N
CN
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Bindels
René J M
RJ
Hoenderop
Joost G J
JG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D005966:Glucuronidase / Q000235:genetics / Q000502:physiology; D006031:Glycosylation; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000502:physiology*; D000090265:Klotho Proteins; D051379:Mice; D008954:Models, Biological; D011493:Protein Kinase C / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology*; D020840:Tissue Kallikreins / Q000502:physiology
D015220:Calcium Channels; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D011493:Protein Kinase C; D005966:Glucuronidase; D000090265:Klotho Proteins; D020840:Tissue Kallikreins; D002118:Calcium