Facilitated calcium diffusion by intestinal calcium-binding protein

Feher, Joseph

doi:10.1152/ajpcell.1983.244.3.c303

Cited by 136 publications

(33 citation statements)

References 23 publications

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“…The apical Ca 2+ influx through TRPV5 initiates the disruption of the actin cytoskeleton and the formation of Ca 2+ -enriched endocytic vesicles, which are transported along the microtubules and some fuse with lysosomes [46]. In a third model, the intracellular diffusion of Ca 2+ is facilitated by the vitamin D 3 -dependent Ca 2+ -binding protein, calbindin-D 28K , in the principal cells of DCT2 and CNT segments [7,20]. Together with parvalbumin, calmodulin, and troponin C, calbindins are Ca 2+ -binding proteins that form a family of proteins with Ca 2+ affinity [15].…”

Section: Introductionmentioning

confidence: 99%

Active Ca2+ reabsorption in the connecting tubule

Boros

Bindels

Hoenderop

2008

Pflugers Arch - Eur J Physiol

114

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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.

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Section: Introductionmentioning

confidence: 99%

Active Ca2+ reabsorption in the connecting tubule

Boros

Bindels

Hoenderop

2008

Pflugers Arch - Eur J Physiol

114

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“…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.…”

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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

103

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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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“…38 The likelihood that calbindin-D9K is also present in the brush border is supported by our demonstration that calcitriol supplementation significantly increases calbindin-D9K content of the brush border in both strains. Thus, calbindin-D9K may participate in calcium transport at this level.…”

Section: Discussionmentioning

confidence: 70%