TY - JOUR
T1 - CRTAP Is Required for Prolyl 3- Hydroxylation and Mutations Cause Recessive Osteogenesis Imperfecta
AU - Morello, Roy
AU - Bertin, Terry K.
AU - Chen, Yuqing
AU - Hicks, John
AU - Tonachini, Laura
AU - Monticone, Massimiliano
AU - Castagnola, Patrizio
AU - Rauch, Frank
AU - Glorieux, Francis H.
AU - Vranka, Janice
AU - Bächinger, Hans Peter
AU - Pace, James M.
AU - Schwarze, Ulrike
AU - Byers, Peter H.
AU - Weis, Mary Ann
AU - Fernandes, Russell J.
AU - Eyre, David R.
AU - Yao, Zhenqiang
AU - Boyce, Brendan F.
AU - Lee, Brendan
N1 - Funding Information:
We thank Dr. Millan Patel for helpful discussions, Dr. Mallein-Gering for kindly providing the MC615 cell line, and Raffaela Arbicò for expert technical assistance. The monoclonal antibody 9E10 was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Dept. of Biological Sciences, Iowa City, IA. This work was supported by NIH grants DE01771 (B.L.), ES11253 (B.L.), HD22657 (B.L., D.E.), AR43510 (B.B.), AR051459 (R.M.), AR37318 (D.E.), AR41223 (P.B.), the Baylor College of Medicine Mental Retardation Developmental Disabilities Research Center (MRDDRC), the Shriners of North America (H.P.B., F.H.G.), and the Osteogenesis Imperfecta Foundation and the Bone Disease Program of Texas (R.M.).
PY - 2006/10/20
Y1 - 2006/10/20
N2 - Prolyl hydroxylation is a critical posttranslational modification that affects structure, function, and turnover of target proteins. Prolyl 3-hydroxylation occurs at only one position in the triple-helical domain of fibrillar collagen chains, and its biological significance is unknown. CRTAP shares homology with a family of putative prolyl 3-hydroxylases (P3Hs), but it does not contain their common dioxygenase domain. Loss of Crtap in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. CRTAP can form a complex with P3H1 and cyclophilin B (CYPB), and Crtap-/- bone and cartilage collagens show decreased prolyl 3-hydroxylation. Moreover, mutant collagen shows evidence of overmodification, and collagen fibrils in mutant skin have increased diameter consistent with altered fibrillogenesis. In humans, CRTAP mutations are associated with the clinical spectrum of recessive osteogenesis imperfecta, including the type II and VII forms. Hence, dysregulation of prolyl 3-hydroxylation is a mechanism for connective tissue disease.
AB - Prolyl hydroxylation is a critical posttranslational modification that affects structure, function, and turnover of target proteins. Prolyl 3-hydroxylation occurs at only one position in the triple-helical domain of fibrillar collagen chains, and its biological significance is unknown. CRTAP shares homology with a family of putative prolyl 3-hydroxylases (P3Hs), but it does not contain their common dioxygenase domain. Loss of Crtap in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. CRTAP can form a complex with P3H1 and cyclophilin B (CYPB), and Crtap-/- bone and cartilage collagens show decreased prolyl 3-hydroxylation. Moreover, mutant collagen shows evidence of overmodification, and collagen fibrils in mutant skin have increased diameter consistent with altered fibrillogenesis. In humans, CRTAP mutations are associated with the clinical spectrum of recessive osteogenesis imperfecta, including the type II and VII forms. Hence, dysregulation of prolyl 3-hydroxylation is a mechanism for connective tissue disease.
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U2 - 10.1016/j.cell.2006.08.039
DO - 10.1016/j.cell.2006.08.039
M3 - Article
C2 - 17055431
AN - SCOPUS:33750207868
SN - 0092-8674
VL - 127
SP - 291
EP - 304
JO - Cell
JF - Cell
IS - 2
ER -