Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 409051
Title Trpv5/6 is vital for epithelial calcium uptake and bone formation
Author(s) Vanoevelen, J.; Janssens, A.; Huitema, L.F.A.; Hammond, C.L.; Metz, J.R.; Flik, G.; Voets, T.; Schulte-Merker, S.
Source FASEB Journal 25 (2011)9. - ISSN 0892-6638 - p. 3197 - 3207.
Department(s) Experimental Zoology
Publication type Refereed Article in a scientific journal
Publication year 2011
Keyword(s) ca2+ channel - in-vivo - stannius corpuscles - cation channels - stanniocalcin 1 - danio-rerio - absorption - zebrafish - transport - receptor
Abstract Calcium is an essential ion serving a multitude of physiological roles. Aside from its role as a second messenger, it is an essential component of the vertebrate bone matrix. Efficient uptake and storage of calcium are therefore indispensable for all vertebrates. Transient receptor potential family, vanilloid type (TRPV)5 and TRPV6 channels are known players in transcellular calcium uptake, but the exact contribution of this pathway is unclear. We used forward genetic screening in zebrafish (Danio rerio) to identify genes essential in bone formation and identified a lethal zebrafish mutant (matt-und-schlapp) with severe defects in bone formation, including lack of ossification of the vertebral column and craniofacial structures. Mutant embryos show a 68% reduction in calcium content, and systemic calcium homeostasis is disturbed when compared with siblings. The phenotype can be partially rescued by increasing ambient calcium levels to 25 mM. We identified the mutation as a loss-of-function mutation in the single orthologue of TRPV5 and 6, trpv5/6. Expression in HEK293 cells showed that Trpv5/6 is a calcium-selective channel capable of inward calcium transport at physiological concentrations whereas the mutant channel is not. Taken together, this study provides both genetic and functional evidence that transcellular epithelial calcium uptake is vital to sustain life and enable bone formation.—Vanoevelen, J., Janssens, A., Huitema, L. F. A., Hammond, C. L., Metz, J. R., Flik, G., Voets, T., Schulte-Merker, S. Trpv5/6 is vital for epithelial calcium uptake and bone formation
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