Active Ca(2+) reabsorption in the connecting tubule.
The kidney plays a crucial role in the maintenance of the body calcium (Ca(2+)) balance. Ca(2+) is an essential ion in all organisms and participates in a large variety of structural and functional processes. In mammals, active tubular Ca(2+) reabsorption is restricted to the distal part of the nephron, i.e., the late distal convoluted (DCT2) and the connecting tubules (CNT), where approximately 10-15% of the total Ca(2+) is reabsorbed. This active transcellular transport is hallmarked by the transient receptor potential vanilloid 5 (TRPV5) epithelial Ca(2+) channel, regulated by an array of events, and mediated by hormones, including 1,25-dihydroxyvitamin D(3), parathyroid hormone, and estrogen. Novel molecular mechanisms have been identified, such as the direct regulatory effects of klotho and tissue kallikrein on the abundance of TRPV5 at the apical membrane. The newly discovered mechanisms could provide potential pharmacological targets in the therapy of renal Ca(2+) wasting. This review discusses the three basic molecular steps of active Ca(2+) reabsorption in the DCT/CNT segments of the nephron, including apical entry, cytoplasmic transport, and basolateral extrusion of Ca(2+). In addition, an overview of the recently identified mechanisms governing this active Ca(2+) transport through the DCT2/CNT epithelial cells will be presented.
Boros
Sandor
S
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
Bindels
René J M
RJ
Hoenderop
Joost G J
JG
D000818:Animals; D017306:Annexin A2 / Q000502:physiology; D001693:Biological Transport, Active; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D022461:Caveolins / Q000502:physiology; D002966:Clathrin / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005959:Glucosidases / Q000502:physiology; D005966:Glucuronidase / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism*; D000090265:Klotho Proteins; D010281:Parathyroid Hormone / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000502:physiology; D009418:S100 Proteins / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology*; D020840:Tissue Kallikreins / Q000502:physiology; D014807:Vitamin D / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000502:physiology; D000099193:rab11 GTP-Binding Proteins; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D064026:Calbindins; D002118:Calcium; D002135:Calcium-Binding Proteins; D022461:Caveolins; D002966:Clathrin; D004967:Estrogens; D005959:Glucosidases; D005966:Glucuronidase; D047908:Intracellular Signaling Peptides and Proteins; D000090265:Klotho Proteins; D010281:Parathyroid Hormone; D019269:Phosphatidylinositol 4,5-Diphosphate; D053499:Plasma Membrane Calcium-Transporting ATPases; D064030:S100 Calcium Binding Protein G; D009418:S100 Proteins; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; D020840:Tissue Kallikreins; D014807:Vitamin D; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; D000099248:S100 Calcium Binding Protein A10; C506952:ATP2B1 protein, human; C492239:TRPV5 protein, human; C110374:sodium-calcium exchanger 1; C070368:PRKCSH protein, human