CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta.

Morello, Roy; Bertin, Terry K; Chen, Yuqing; Hicks, John; Tonachini, Laura; Monticone, Massimiliano; Castagnola, Patrizio; Rauch, Frank; Glorieux, Francis H; Vranka, Janice; Bächinger, Hans Peter; Pace, James M; Schwarze, Ulrike; Byers, Peter H; Weis, MaryAnn; Fernandes, Russell J; Eyre, David R; Yao, Zhenqiang; Boyce, Brendan F; Lee, Brendan

Morello, Roy; Bertin, Terry K; Chen, Yuqing; Hicks, John; Tonachini, Laura; Monticone, Massimiliano; Castagnola, Patrizio; Rauch, Frank; Glorieux, Francis H; Vranka, Janice; Bächinger, Hans Peter; Pace, James M; Schwarze, Ulrike; Byers, Peter H; Weis, MaryAnn; Fernandes, Russell J; Eyre, David R; Yao, Zhenqiang; Boyce, Brendan F; Lee, Brendan.

Afiliación

Morello R; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Cell ; 127(2): 291-304, 2006 Oct 20.

Article en En | MEDLINE | ID: mdl-17055431

RESUMEN

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.

Asunto(s)

Proteínas de la Matriz Extracelular/metabolismo; Mutación; Osteogénesis Imperfecta/genética; Procolágeno-Prolina Dioxigenasa/metabolismo; Proteínas/metabolismo; Secuencia de Aminoácidos; Animales; Enfermedades Óseas Metabólicas/genética; Enfermedades Óseas Metabólicas/metabolismo; Enfermedades Óseas Metabólicas/patología; Huesos/embriología; Huesos/metabolismo; Huesos/patología; Células Cultivadas; Análisis Mutacional de ADN; Proteínas de la Matriz Extracelular/genética; Colágenos Fibrilares/metabolismo; Fibroblastos/metabolismo; Humanos; Ratones; Ratones Endogámicos C57BL; Ratones Noqueados; Chaperonas Moleculares; Datos de Secuencia Molecular; Osteocondrodisplasias/genética; Osteocondrodisplasias/metabolismo; Osteocondrodisplasias/patología; Osteogénesis Imperfecta/metabolismo; Proteínas/genética; ARN Mensajero/metabolismo; Factores de Tiempo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis Imperfecta / Proteínas / Proteínas de la Matriz Extracelular / Procolágeno-Prolina Dioxigenasa / Mutación Límite: Animals / Humans Idioma: En Revista: Cell Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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