Role of Cartilage-Associated Protein in Skeletal Development
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The past 3 years have been exciting for collagen biologists and human geneticists studying the disease known as osteogenesis imperfecta (OI or brittle bone disease). Functional studies on cartilage-associated protein (Crtap) have identified it as an essential component of a heterotrimeric, endoplasmic reticulum resident complex responsible for collagen prolyl 3-hydroxylation and chaperone function. Importantly, human mutations in the CRTAP gene have been associated with recessive forms of OI. Although the function and in vivo biological significance of the 3-hydroxyproline modification are still poorly understood, studies on Crtap have led to the identification of additional genes in which mutations also cause recessive forms of OI. These discoveries have now focused the interest of geneticists on the endoplasmic reticulum that will require the help of biochemists to unravel the molecular dynamics and complexities of collagen folding.
KeywordsCartilage-associated protein Crtap mutations Skeletal development Osteogenesis imperfecta
The authors would like to thank David R. Eyre (Seattle, WA) and Dustin Baldridge (Houston, TX) for their insightful comments. This research was supported in part by the National Institute of Health grant AR051459 (Dr. Roy Morello), the Osteogenesis Imperfecta Foundation and the Rolanette and Berdon Lawrence Bone Disease Program of Texas (Dr. Roy Morello) and by the Shriners of North America (Dr. Frank Rauch). Dr. Rauch is a Chercheur-Boursier Clinicien of the Fonds de la Recherche en Santé du Québec.
No potential conflicts of interest relevant to this article were reported.
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