Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5

Topala, Catalin N.; Schoeber, Joost P. H.; Searchfield, Lydia; Riccardi, Daniela; Hoenderop, Joost G. J.; Bindels, René J. M.

doi:10.1016/j.ceca.2008.12.003

Cited by 88 publications

(67 citation statements)

References 32 publications

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“…These data suggest that Trpv5/6 represses IGF signaling and suppresses NaR cell proliferation under normal 27 Activation of CaSR has been shown to increase mammalian TRPV5 activity. 38 This possibility was not supported by our data. Addition of a CaSR antagonist did not affect basal or Ca 2 þ deficiency-induced Akt signaling in human Caco-2 cells or in NaR cells.…”

Section: Discussioncontrasting

confidence: 56%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2 þ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2 þ -transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2 þ ] environments. BrdU pulse-labeling experiments suggest that low [Ca 2 þ ] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2 þ ] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2 þ -selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2 þ ]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2 þ ]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2 þ ]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2 þ ]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2 þ ]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2 þ ] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2 þ deficiency.

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Section: Discussioncontrasting

confidence: 56%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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“…Ca 2ϩ then leaves the cell via extrusion through the Na ϩ /Ca 2ϩ exchanger NCX1 and the plasma membrane Ca 2ϩ -ATPase PMCA1b (69). The CaSR is present on the basolateral cell surface and intracellularly in rat DCT (135); it is also expressed apically, in a punctuate pattern, in the human DCT (155). Using immunohistochemistry on frozen sections from human kidney tissue, Topala et al (155) reported colocalization of CaSR with TRPV5 at the apical membrane and in subapical vesicles of DCT and CNT cells.…”

Section: Casr and The Kidneymentioning

confidence: 99%

“…The CaSR is present on the basolateral cell surface and intracellularly in rat DCT (135); it is also expressed apically, in a punctuate pattern, in the human DCT (155). Using immunohistochemistry on frozen sections from human kidney tissue, Topala et al (155) reported colocalization of CaSR with TRPV5 at the apical membrane and in subapical vesicles of DCT and CNT cells. In cell lines overexpressing TRPV5 (or TRPV6) and CaSR, receptor activation increased the activity of TRPV5, but not that of its close homolog TRPV6.…”

Section: Casr and The Kidneymentioning

confidence: 99%

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

Riccardi

Brown

2010

American Journal of Physiology-Renal Physiology

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296

239

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“…Biotin was then coupled to streptavidin-HRP and visualized with Thyramid (TSA Fluorescein System, NEL701A001KT; PerkinElmer Life Sciences). TRPV5 staining was described previously (4). Negative controls, i.e.…”

Section: Methodsmentioning

confidence: 99%

β1-Adrenergic Receptor Signaling Activates the Epithelial Calcium Channel, Transient Receptor Potential Vanilloid Type 5 (TRPV5), via the Protein Kinase A Pathway

Hagen¹,

Tudpor²,

Verkaart

et al. 2014

Journal of Biological Chemistry

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Background: ␤1-Adrenergic receptors (␤-ARs) are expressed in the distal part of the nephron where TRPV5-mediated active Ca 2ϩ reabsorption takes place. Results: The ␤1-AR agonist dobutamine, by inducing PKA-dependent phosphorylation, enhanced influx of Ca 2ϩ through TRPV5. Conclusion: ␤1-AR signaling potentially stimulates transcellular Ca 2ϩ transport in the kidney. Significance: Dobutamine, generally used as a positive inotrope, probably also has a calciotropic effect.

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Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5

Cited by 88 publications

References 32 publications

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

β1-Adrenergic Receptor Signaling Activates the Epithelial Calcium Channel, Transient Receptor Potential Vanilloid Type 5 (TRPV5), via the Protein Kinase A Pathway

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