Ca2+ Dependence of the Ca2+-selective TRPV6 Channel

Bödding, Matthias; Flockerzi, Veit

doi:10.1074/jbc.m404679200

Cited by 61 publications

(52 citation statements)

References 20 publications

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“…The inactivation of TRPV6 is characterized by a slow decline after an initial fast inactivation phase, whereas TRPV5 only shows the slow inactivation phase (Nilius et al 2001a. In line with a Ca 2+ -dependent regulation is the observation that chelation of intracellular Ca 2+ with ethylene glycol-bis(b-aminoethyl ether)-N,N,N′,N′-tetra acetic acid (EGTA) or 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acethoxymethylester (BAPTA) resulted in increased channel activity (Bodding and Flockerzi 2004;Hoenderop et al 2001b;Peng et al 1999). Together, these data indicate that intracellular Ca 2+ exerts a negative feedback mechanism on TRPV5 and TRPV6 activity.…”

Section: Ca 2+ -Dependent Inactivationmentioning

confidence: 88%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The epithelial Ca 2+ channels TRPV5 and TRPV6 represent a new family of Ca 2+ channels that belongs to the superfamily of transient receptor potential channels. TRPV5 and TRPV6 constitute the apical Ca 2+ entry mechanism in active Ca 2+ transport in kidney and intestine. The central role of TRPV5 and TRPV6 in active Ca 2+ (re)absorption makes it a prime target for regulation to maintain Ca 2+ balance. This review covers the hormonal regulation, interaction with accessory proteins and (patho)physiological implications of these epithelial Ca 2+ channels.

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Section: Ca 2+ -Dependent Inactivationmentioning

confidence: 88%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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“…A recent study reported that IGF-1 is secreted by Ca 2 þ -triggered exocytosis 24 it was later shown that this is likely due to an effect of fura-2 in buffering intracelluar [Ca 2 þ ], because patch-clamp recording indicated no spontaneous channel activity. 41 It is now understood that TRPV5/6 channels are negatively regulated by extracellular [Ca 2 þ ], and that lowering extracellular [Ca 2 þ ] can increase the channel conductance to monovalent cations such as Na þ . 24,40,42 Membrane depolarization has been shown to activate the PI3K-Akt signaling in neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

“…Immunoprecipitation was performed using the 4G10 or anti-p85 antibodies following previously published protocol. 41 The immunoprecipitated complex was analyzed by western blot using anti-p85, anti-PDK1, and 4G10 antibodies as described above. The ratios of phosphorylated to total protein were calculated after the images had been analyzed by densitometry using a Fluor-S Imager (Bio-Rad) and ImageJ software.…”

Section: Discussionmentioning

confidence: 99%

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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“…Furthermore, even high concentrations of fast exogenous Ca 2ϩ chelators are unable to control the microdomain in the close proximity of the channel (9). Thus, the physiological activation mechanism of TRPV6 is not clear because no current was detected under in vivo Ca 2ϩ buffering conditions (10).…”

Section: The Transient Receptor Potential (Trp)mentioning

confidence: 99%