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Trpv6  -  transient receptor potential cation...

Mus musculus

Synonyms: CAT, CaT1, Cac, Calcium transport protein 1, ECaC2, ...
 
 
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Disease relevance of Trpv6

 

High impact information on Trpv6

  • The calcium transport protein1 (CaT1) was more abundantly expressed at mRNA level than the epithelial calcium channel (ECaC) in duodenum, but both were considerably reduced (CaT1>90%, ECaC>60%) in the two VDR-KO strains on a normal calcium diet [3].
  • Both channels retained their phenotype after exchanging the complete N termini, the C termini, or even both N and C termini, i.e. ECaC1 with the ECaC2 N or C terminus still showed the ECaC1 phenotype and vice versa [4].
  • However, the kinetics of ECaC2 currents notably differ from ECaC1 currents [4].
  • Trpv6 encodes a Ca(2+)-permeable cation channel responsible for vitamin D-dependent intestinal Ca(2+) absorption [1].
  • In addition to their deranged Ca(2+) homeostasis, the skin of Trpv6 KO mice has fewer and thinner layers of stratum corneum, decreased total Ca(2+) content, and loss of the normal Ca(2+) gradient [1].
 

Biological context of Trpv6

  • Although our Trpv6 KO affects the closely adjacent EphB6 gene, the phenotype reported here is not related to EphB6 dysfunction [1].
  • CaT1 expression is reduced in ERKOalpha mice and induced by estrogen treatment, pregnancy, or lactation in VDR WT and KO mice [5].
  • CONCLUSIONS: Estrogens or hormonal changes during pregnancy or lactation have distinct, vitamin D-independent effects at the genomic level on active duodenal calcium absorption mechanisms, mainly through a major upregulation of the calcium influx channel CaT1 [5].
  • Our data demonstrate that higher CaBP levels do not ensure high rates of duodenal Ca absorption and that transcellular Ca absorption can occur even when ECaC2 gene expression is very low [6].
  • 4. Calcium transport activity was only 9.7 and 8.7% of adult frog levels in plasma membranes isolated from the livers of tadpoles without and with limbs, respectively [7].
 

Anatomical context of Trpv6

 

Associations of Trpv6 with chemical compounds

  • In addition, the kidneys and bones of Trpv6 KO mice do not respond to their elevated levels of PTH and 1,25-dihydroxyvitamin D [1].
  • Trpv6 KO mice have normal urinary deoxypyridinoline excretion, although exhibiting a 9.3% reduction in femoral mineral density at 2 months of age, which is not restored by treatment for 1 month with a high (2%) Ca(2+) "rescue" diet [1].
  • Interestingly, ECaC2 has a 100-fold lower affinity for ruthenium red (IC(50) 9 +/- 1 microM) than ECaC1 (IC(50) 121 +/- 13 nM) [8].
  • Calcium transport, thiol status, and hepatotoxicity following N-nitrosodimethylamine exposure in mice [12].
 

Regulatory relationships of Trpv6

  • Our data indicate that CaT1 and ECaC mRNA levels are differentially regulated by 1,25(OH)(2)D(3) in kidney and intestine and that there may be a specialized role for CaT1 in kidney in fetal and neonatal development [13].
 

Other interactions of Trpv6

  • We report the phenotype of mice with targeted disruption of the Trpv6 (Trpv6 KO) epithelial calcium channel [1].
  • Long- and short-term adaptation to changes in dietary calcium (Ca) level and 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] injection strongly regulated duodenal calbindin D(9k) and CaT1 mRNA [13].
  • In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-) mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this response [14].
  • 1. Plasma membranes of comparable yield and purity were isolated from the livers of various animal species belonging to phylogenetic groups from Amphibia to Mammalia. 2. Calcium transport activity was observed in all liver plasma membranes examined [7].
 

Analytical, diagnostic and therapeutic context of Trpv6

  • Southern blot analysis demonstrated that this family is restricted to two members, ECaC1 and ECaC2 (also named CaT1) [8].
  • Ovariectomy caused no change in duodenal expression pattern of VDR WT and KO mice, whereas treatment with a pharmacologic dose of estrogens induced CaT1 mRNA expression in VDR WT (4-fold) and KO (8-fold) mice [5].

References

  1. Marked disturbance of calcium homeostasis in mice with targeted disruption of the trpv6 calcium channel gene. Bianco, S.D., Peng, J.B., Takanaga, H., Suzuki, Y., Crescenzi, A., Kos, C.H., Zhuang, L., Freeman, M.R., Gouveia, C.H., Wu, J., Luo, H., Mauro, T., Brown, E.M., Hediger, M.A. J. Bone Miner. Res. (2007) [Pubmed]
  2. Calcium transport by Ehrlich ascites cell mitochondria in vitro and in situ. Cockrell, R.S. Arch. Biochem. Biophys. (1981) [Pubmed]
  3. Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Van Cromphaut, S.J., Dewerchin, M., Hoenderop, J.G., Stockmans, I., Van Herck, E., Kato, S., Bindels, R.J., Collen, D., Carmeliet, P., Bouillon, R., Carmeliet, G. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Fast and slow inactivation kinetics of the Ca2+ channels ECaC1 and ECaC2 (TRPV5 and TRPV6). Role of the intracellular loop located between transmembrane segments 2 and 3. Nilius, B., Prenen, J., Hoenderop, J.G., Vennekens, R., Hoefs, S., Weidema, A.F., Droogmans, G., Bindels, R.J. J. Biol. Chem. (2002) [Pubmed]
  5. Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms. Van Cromphaut, S.J., Rummens, K., Stockmans, I., Van Herck, E., Dijcks, F.A., Ederveen, A.G., Carmeliet, P., Verhaeghe, J., Bouillon, R., Carmeliet, G. J. Bone Miner. Res. (2003) [Pubmed]
  6. Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. Song, Y., Kato, S., Fleet, J.C. J. Nutr. (2003) [Pubmed]
  7. Calcium transport activities of plasma membranes isolated from the livers of various animal species. Sulakhe, S.J., Pulga, V.B., Tran, S.T. Comparative biochemistry and physiology. A, Comparative physiology. (1990) [Pubmed]
  8. Function and expression of the epithelial Ca(2+) channel family: comparison of mammalian ECaC1 and 2. Hoenderop, J.G., Vennekens, R., Müller, D., Prenen, J., Droogmans, G., Bindels, R.J., Nilius, B. J. Physiol. (Lond.) (2001) [Pubmed]
  9. Phenytoin: effects on calcium flux and cyclic nucleotides. Ferrendelli, J.A., Kinscherf, D.A. Epilepsia (1977) [Pubmed]
  10. Calcium transport in and out of brain nerve endings in vitro--the role of synaptosomal plasma membrane Ca2+-ATPase in Ca2+-extrusion. Lin, S.C., Way, E.L. Brain Res. (1984) [Pubmed]
  11. Calcium transport and phosphoenzyme formation in dystrophic mouse sarcoplasmic reticulum. Mrak, R.E., Baskin, R.J. Biochemical medicine. (1978) [Pubmed]
  12. Calcium transport, thiol status, and hepatotoxicity following N-nitrosodimethylamine exposure in mice. Reitman, F.A., Berger, M.L., Minnema, D.J., Shertzer, H.G. Journal of toxicology and environmental health. (1988) [Pubmed]
  13. Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Song, Y., Peng, X., Porta, A., Takanaga, H., Peng, J.B., Hediger, M.A., Fleet, J.C., Christakos, S. Endocrinology (2003) [Pubmed]
  14. Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. Tenenhouse, H.S., Gauthier, C., Martel, J., Hoenderop, J.G., Hartog, A., Meyer, M.H., Meyer, R.A., Bindels, R.J. Pflugers Arch. (2002) [Pubmed]
 
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