Vitamin D-stimulated intestinal calcium absorption may not involve calcium-binding protein directly

Spencer, Rosemary; Charman, M.; Wilson, Peter W.F.; Lawson, E.

doi:10.1038/263161a0

Cited by 137 publications

(31 citation statements)

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“…This observation is consistent with those made in chicks and rats. Spencer et al (33) showed that after 1,25(OH) 2 D 3 injection in rachitic chicks, both calcium absorption and calbindin D 28k proteins were elevated. However, while calbindin D 28k remained elevated for 32 h after its peak induction, a high rate of calcium absorption was not maintained during that same period, falling to 25% of its maximum rate.…”

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

102

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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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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

102

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“…This role could involve interacting with other proteins, or facilitating calcium diffusion (10,39), or providing shortterm buffering for local calcium concentration in the cytosol. A calcium-buffering role in neurons has been suggested both for calbindin (5,29,30) and for parvalbumin (9,13,18), by analogy with evidence that they have calcium-buffeting roles respectively in intestinal calcium absorption (60) and in muscle contraction (26,48).…”

Section: Function Of Cabps In Neuronsmentioning

confidence: 99%

Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons [published erratum appears in J Cell Biol 1990 May;110(5):1845]

Rogers

1987

The Journal of Cell Biology

558

296

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Abstract.A novel gene of the calmodulin superfamily, encoding a 29-kD neuronal protein here named "calretinin; has been isolated as a cDNA clone from chick retina. The encoded sequence includes four putative calcium-binding sites and a fusion protein binds calcium. The most similar protein known is the 28-kD intestinal calcium-binding protein, calbindin (58% homology). Both genes date from before the divergence of chicks from mammals. The distribution of calretinin and calbindin mRNAs in chick tissues has been mapped using RNA gel blots and in situ hybridization. RNAs from both genes are abundant in the retina and in many areas of the brain, but calretinin RNA is absent from intestine and other nonneural tissues. Calretinin and calbindin are expressed in different sets of neurons throughout the brain. Calretinin RNA is particularly abundant in auditory neurons with precisely timed discharges.T HE superfamily of calcium-binding proteins, whose prototype is calmodulin, contains at least a dozen members which perform a wide variety of calciumdependent functions in different tissues. Calmodulin itself regulates several important enzymes in most cell types (34). Troponin C and the myosin light chains regulate muscle contraction (1). Parvalbumin, another muscle protein, appears to be involved in terminating fast contractions (26). Another important member of the superfamily is the 28-kD vitamin D-dependent intestinal calcium-binding protein (70), also known as cholecalcin 28k, spot 35, or visinin (47a), and now re-named calbindin DEak-hereafter "calbindin." Calbindin appears to be involved in intestinal calcium transport, but is also present in kidney, bone, and several other tissues (30,46,65). The calbindin gene has been cloned by several groups (21,27,28,71,72).Many neurons in the brains of mammals and of birds exhibit immunoreactivity for parvalbumin (7,9,13,15,17,18) or for calbindin (5,20,22,29,30,33,57). Each is present only in some neurons, commonly throughout the whole neuron including the dendritic tree and axonal terminals. They are both very abundant in the Purkinje cells of the cerebellum, and calbindin constitutes "~15 % of the soluble protein of these cells (5, 6,30,40,47,64). But elsewhere in the brain, calbindin and parvalbumin immunoreactivities are mostly in separate neurons (9,11,24). Both are also present in rat retina (17,50), and calbindin immunoreactivity is present in chick retina (25,53,58).The function of these proteins in neurons is unknown. An initial suggestion that parvalbumin was colocalized with GABA (15) has not been generally confirmed by more extensive surveys (13, 18). Parvalbumin-containing neurons do generally have rapid firing rates (9, 14). The numerous calbindin-immunoreactive cells are not known to have any common features.I now report the isolation from chick retina of an mRNA encoding a new member of the superfamily, which is expressed in the retina and in brain neurons. Because of its homology with calcium-binding proteins and its tissue of origin, I refer to the encoded p...

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“…In avian intestine, calbindin is induced by vitamin D and is associated with calcium absorption, though some studies indicate that calcium absorption can precede calbindin induction [21]. Calbindin proposed to facilitate calcium diffusion across the cells by greatly increasing the cytosolic calcium capacity [22, 231.…”

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confidence: 99%

“…Calbindin D28k (calbindin) is also found in many neurons [ 13 -181, but is also present in several epithelia tissues involved in calcium transport, including renal tubules and (in birds) the intestinal epithelium [19, 201. The functions of calretinin and calbindin are uncertain. In avian intestine, calbindin is induced by vitamin D and is associated with calcium absorption, though some studies indicate that calcium absorption can precede calbindin induction [21]. Calbindin proposed to facilitate calcium diffusion across the cells by greatly increasing the cytosolic calcium capacity [22,231.…”

mentioning

confidence: 99%

Calcium binding by chick calretinin and rat calbindin D28k synthesised in bacteria

Cheung

Richards

Rogers

1993

European Journal of Biochemistry

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Calretinin is a member of the EF-hand calcium-binding protein family, with a high similarity with calbindin D28k. The chick calretinin cDNA sequence was reconstructed in a M13 vector and transferred into an expression plasmid derived from the PET series. The calretinin gene was expressed in Escherichia coli and produced immunoreactive calretinin of the expected size. Bacterially expressed calretinin was purified with successive ammonium-sulfate precipitation, DEAE chromatography, hydroxyapatite chromatography, Sephadex G-75 chromatography and Mono-Q chromatography. Normally, 1 .O-1.5 mg calretinin was obtained from 1 1 bacterial culture with a protein recovery of 0.5 -1.5%. Calbindin D28k was purified similarly from bacteria using an expression plasmid provided by W. Hunziker. Calcium-binding activity of purified proteins was measured by equilibrium dialysis in calcium/EGTA mixtures with 45Ca as tracer. Both calretinin and calbindin D28k bound 3 -4 Ca2+/molecule (calretinin, 4.0 2 0.5 ; calbindin D28k, 3.5 2 0.4), implying that at least one of the canonical EF-hand domains does not bind calcium. The Kd was 0.3-0.5 pM with little difference between the values for the two proteins.Calretinin and calbindin D28k are two calcium-binding proteins present in the cytosol of different (though overlapping) sets of cells in vertebrates. They are closely related members of the EF hand superfamily, which includes calcium-dependent regulatory proteins such as calmodulin as well as calcium-buffering proteins such as parvalbumin [ l -61. Calretinin is mainly found in a variety of neurons 17-141, although it is also present in developing rat ovary [15]. Calbindin D28k (calbindin) is also found in many neurons [ 13 -181, but is also present in several epithelia tissues involved in calcium transport, including renal tubules and (in birds) the intestinal epithelium [19, 201.The functions of calretinin and calbindin are uncertain. In avian intestine, calbindin is induced by vitamin D and is associated with calcium absorption, though some studies indicate that calcium absorption can precede calbindin induction [21]. Calbindin proposed to facilitate calcium diffusion across the cells by greatly increasing the cytosolic calcium capacity [22, 231. In neurons, calbindin would be expected to bind the majority of calcium that enters the cytosol, and thereby to affect various calcium-dependent processes involved in neuronal signalling. Whether it also regulates any other proteins directly, in the manner of calmodulin [ l ] or recoverin [24, 251, is unknown. The same questions apply to calretinin. Nore. The chick calretinin nucleotide sequence has been deposited with the EMBL library, submission number X62866. Downing St., Cambridge, England CB2 3EGThe complete amino acid sequences of calretinin and calbindin from chicks and mammals (predicted from cDNA sequences) are aligned in Fig. 1. Each protein has six EF-hand domains, although the sixth is aberrant [9,12,[26][27][28]. The predicted chick calretinin sequence has 268 amino acids (not ...

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Vitamin D-stimulated intestinal calcium absorption may not involve calcium-binding protein directly

Cited by 137 publications

References 20 publications

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

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

Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons [published erratum appears in J Cell Biol 1990 May;110(5):1845]

Calcium binding by chick calretinin and rat calbindin D28k synthesised in bacteria

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