Molecular Cloning, Tissue Distribution, and Chromosomal Mapping of the Human Epithelial Ca2+ Channel (ECAC1)

Müller, Dominik; Hoenderop, Joost G. J.; Meij, Iwan C.; Heuvel, L. P. J. Van Den; Knoers, Nine V A M; Hollander, Anneke I. den; Eggert, Paul; García‐Nieto, Victor; Claverie-Martı́n, Félix; Bindels, René J. M.

doi:10.1006/geno.2000.6203

Cited by 132 publications

(90 citation statements)

References 22 publications

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“…ECaC RNA is present in duodenum at very high levels and is found as well in the jejunum, kidney, and placenta (39). In the rabbit duodenum, ECaC protein is present in high levels in villus tips, whereas it is virtually absent from crypts, a pattern similar to that seen for CaT1 (48 (55), and ECAC2 is nearby at 7q34-q35 (45). The gene for PCMA1 is located at 12q21-23 (56), and calbindin-D 9k is on the X chromosome (57).…”

mentioning

confidence: 62%

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

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mentioning

confidence: 62%

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

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“…In 1999, Hoenderup et al (16) and Peng et al (28) identified two closely related calcium channels from mammalian intestine, ECaC and CaT1, respectively. ECaC mRNA is reported to be highly expressed in human small intestine, kidney, and pancreas but less strongly expressed in tissues like distal colon (22). It has an apical localization and is coexpressed with calbindin D 9k and PMCA in rabbit intestinal cells (15).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D-inducible calcium transport and gene expression in three Caco-2 cell lines

Fleet

Eksir

Hance

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

101

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The parental cell line (P) of Caco-2 cells and two clones, BBe and TC7, were studied at 11 days postconfluence to test the facilitated diffusion model of vitamin D-mediated intestinal calcium absorption (CaTx). Nuclear vitamin D receptor (nVDR) and calbindin D 9k (CaBP) were measured by Western blot; 1,25-hydroxyvitamin D 3 24-hydroxylase (CYP24), CaBP, plasma membrane Ca-ATPase (PMCA), and Ca transport channel (CaT1) mRNA levels were examined by RT-PCR; and net apical-to-basolateral CaTx was examined after treating cells with vehicle or 10 nM calcitriol for 8 (mRNA levels) or 48 h (protein, CaBP mRNA, CaTx). nVDR level was lowest in BBe (38% P value) and directly related to CYP24 induction (TC7 ϭ P, which were 1.56 times greater than BBe). nVDR was inversely related to the vitamin D-induced levels of CaT1 mRNA, CaBP mRNA, PMCA mRNA, and net CaTx, with the highest induction seen in BBe. Basal CaBP mRNA (86 times greater than P) and protein levels were highest in TC7 cells and were not associated with higher net CaTx, suggesting CaBP may not be rate limiting for CaTx in these cells.intestine; calcium absorption; calbindin D 9k; calcium transport channel; plasma membrane Ca-adenosinetriphosphatase INTESTINAL CALCIUM ABSORPTION and its regulation by vitamin D status have been studied for over 60 years (26). The active metabolite that controls this process is 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] (27). To date, two models have been proposed to explain this process: the facilitated diffusion model (2) and the vesicular model (23). In the facilitated diffusion model, summarized in Fig. 1, the basal rate of calcium uptake and calcium extrusion from the absorptive epithelial cell is proposed to be sufficient to accommodate the elevated rate of transport seen after vitamin D stimulation. In contrast, mathematical modeling shows that intracellular diffusion is the rate-limiting, as well as the most vitamin D responsive, step. Calbindin D 9k has been proposed as the protein that binds calcium and facilitates its diffusion between the apical and basolateral surfaces of the cell (8). The level of calbindin D 9k in the intestine is closely correlated with the efficiency of calcium absorption (2), and thus this protein plays a central role in the facilitated diffusion model. In the vesicular model, the cell uses lysosomes to sequester calcium and facilitate its movement to the basolateral membrane for extrusion (24). While calbindin D 28k (the form found in avian intestine) has been associated with lysosomes (25), the role of calbindin in this model is less clear. In the past, we have tested the facilitated diffusion model using cultures of the colonic carcinoma cell line Caco-2 (9, 11, 12, 32).Caco-2 cells are a human colon adenocarcinoma cell line that can spontaneously differentiate in culture and acquire a small intestinal phenotype, e.g., they become polarized columnar epithelial cells, they form tight junctions and domes, and they express several markers that are unique to differentiated small intestinal epithelium...

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“…In human, both channels are coexpressed in organs that mediate transcellular Ca 2+ transport such as duodenum, jejunum, colon, and kidney, but also in pancreas, prostate, mammary, sweat and salivary gland (Hirnet et al 2003;Hoenderop et al 1999Hoenderop et al , 2000aJanssen et al 2002;Muller et al 2000a;Peng et al 1999Peng et al , 2000Peng et al , 2001aWeber et al 2001;Wissenbach et al 2001;Zhuang et al 2002). In general, TRPV5 seems to be the major isoform in kidney, whereas TRPV6 is more ubiquitously expressed with the highest concentrations in the prostate, stomach, brain, lung and small intestine.…”

Section: Molecular Features Of Trpv5 and Trpv6mentioning

confidence: 99%

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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Molecular Cloning, Tissue Distribution, and Chromosomal Mapping of the Human Epithelial Ca2+ Channel (ECAC1)

Cited by 132 publications

References 22 publications

Molecular Mechanisms of Primary Hypercalciuria

Molecular Mechanisms of Primary Hypercalciuria

Vitamin D-inducible calcium transport and gene expression in three Caco-2 cell lines

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

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