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Trpv5/6 is vital for epithelial calcium uptake and bone formation
Author(s) -
Vanoevelen Jo,
Janssens Annelies,
Huitema Leonie F. A.,
Hammond Christina L.,
Metz Juriaan R.,
Flik Gert,
Voets Thomas,
SchulteMerker Stefan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-183145
Subject(s) - calcium , trpv6 , microbiology and biotechnology , transcellular , zebrafish , transient receptor potential channel , calcium metabolism , calcium channel , mutant , biology , trpv4 , chemistry , endocrinology , genetics , receptor , gene , organic chemistry
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. FASEB J. 25, 3197‐3207 (2011). www.fasebj.org