Collagen is an extracellular matrix
protein that serves as a scaffold defining the shape and mechanical properties of many tissues and organs including skin, tendon, artery walls, fibrocartilage, bone and teeth. Collagens are highly conserved and are characterized by an uninterrupted "Glycine X Y" triplet repeat that is a necessary part of the triple helical structure. The extensive family of collagens is composed of several chain types, including fibril-forming interstitial collagens (types I, II
) and basement membrane collagens (type IV
), each type containing multiple isoforms. Collagen type I
(also known as collagen alpha, COL1A1, and alpha-1 type I collagen) is the largest component of fibrillar collagen found in cartilage and connective tissues. It is synthesized by fibroblasts
, osteoblasts, and odontoblasts and has a theoretical molecular weight of 138 kDa.
Type I collagen is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon tissue. Collagens are fibrous, extracellular matrix proteins with high tensile strength and are the major components of connective tissue. Several collagens play a role in cell adhesion, responsible for maintaining normal tissue architecture and function. All collagens contain a triple helix domain and frequently show lateral self-association in order to form complex connective tissues. Post-Golgi
LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues (1).
The COL1A1 gene encodes the pro-alpha1 chains of type I collagen protein, whose triple helix is comprised of two alpha1 chains and one alpha2 chain. Mutations in the encoding COL1A1 gene are associated with brittle bone disease (Osteogenesis Imperfecta), cortical hyperostosis (Caffey disease) and disorders that affect the connective tissues (Ehlers-Danlos syndrome) (2). Studies have found that HIF-1
transcription regulation of collagen prolyl hydroxylases regulates collagen deposition, promoting cancer
cell alignment along collagen fibers, which enhances invasion and metastasis
to lymph nodes and lung tissue by breast cancer cells (3).
1. Banushi, B., Forneris, F., Straatman-Iwanowska, A., Strange, A., Lyne, A. M., Rogerson, C., . . . Gissen, P. (2016). Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis. Nat Commun, 7, 12111. doi:10.1038/ncomms12111
2. Lu, Y., Zhang, S., Wang, Y., Ren, X., & Han, J. (2019). Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen. Intractable Rare Dis Res, 8(2), 98-107. doi:10.5582/irdr.2019.01064
3. Gilkes, D. M., Chaturvedi, P., Bajpai, S., Wong, C. C., Wei, H., Pitcairn, S., . . . Semenza, G. L. (2013). Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Res, 73(11), 3285-3296. doi:10.1158/0008-5472.Can-12-3963