CANTY, E.G.*; KADLER, K.E.: Studies of the role of protein trafficking on collagen fibril assembly in tendon.

Tendon morphogenesis requires the formation of an extracellular matrix (ECM) containing collagen fibrils. How embryonic tendon fibroblasts achieve this elaborate organisation is unknown. We have shown that tendon fibroblasts synthesise ~1 um long early collagen fibrils that fuse tip-to-tip (1) and tip-to-side fusion (2) to produce a fibrous network. The formation of this network, which is hierarchical and under cellular control, produces fibrils that are comprised of helical microfibrils (3), and is a paradigm for the assembly of other fibrous assemblies, including fibrillin (4). Tendon fibroblasts secrete collagen fibrils into crypts formed between the Golgi apparatus and the plasma membrane. Our work is studying how how proteins are targeted to crypts and is of relevance to tendon tissue assembly, in health and disease. References: (1) Graham et al. (2000) Identification of collagen fibril fusion during vertebrate tendon morphogenesis. The process relies on unipolar fibrils and is regulated by collagen-proteoglycan interaction. Journal of Molecular Biology 295: 891-902. (2) Kadler et al. (2000) Tip-mediated fusion involving unipolar collagen fibrils accounts for rapid fibril elongation, the occurrence of fibrillar branched networks in skin and the paucity of collagen fibril ends in vertebrates. Matrix Biology 19: 359-365. (3) Holmes et al. (2001) Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organisation. Proceedings of the National Academy of Sciences U. S. A. 98: 7307-7312. (4) Baldock et al. (2001) The supramolecular organisation of fibrillin-rich microfibrils. Journal of Cell Biology 152: 1045-1056.