DDRs and Collagen Fibrillogenesis

Collagen type I in its mature fibrillar state is the major component of the extracellular matrix (ECM) in a variety of vertebrate tissues. The assembly of collagen fibrils (fibrillogenesis) is a complex process regulated in part by certain collagen-binding proteins (CBPs), which directly interact with the collagen molecules and/or fibrils. Discoidin domain receptors (DDR1 and DDR2) are CBPs, which belong to the family of receptor tyrosine kinases and bind to and get activated by collagen(s), including collagen type I. DDRs are unique in the aspect that their collagen-binding extracellular domain exists both as a cell surface anchored and as a soluble protein in the ECM. Understanding the modulation of collagen fibrillogenesis by DDRs can help provide novel insights into cell−matrix interactions, ECM remodeling, and receptor function.