The
matrilins form a family of oligomeric extracellular adaptor
proteins that are most strongly expressed in cartilage but also present in many other extracellular matrices.
Matrilins bind to different types of
collagen fibrils, to other noncollagenous
proteins and to
aggrecan. They thereby support matrix assembly by connecting fibrillar components and mediating interactions between these and the
aggrecan gel. The binding avidity of a matrilin can be varied by alternative splicing, proteolytic processing and formation of homo- and heterooligomers. Such changes in matrilin structure may lead to a modulation of extracellular matrix assembly. Some
matrilins bind weakly to α1β1
integrin and cell surface
proteoglycans, but even though
matrilins play a role in mechanotransduction and
matrilin-3 activates the expression of
osteoarthritis-associated genes the physiological relevance of matrilin-cell interactions is unclear. Matrilin knockout mice do not display pronounced phenotypes, which points to a redundancy within the
protein family or with functionally related
proteins. In man, dominant mutations in the
von Willebrand factor A like domain of
matrilin-3 lead to a
protein retention in the endoplasmic reticulum that causes
multiple epiphyseal dysplasia by initiating a cell stress response. In contrast, a mutation in an
EGF domain of
matrilin-3 that is associated with hand
osteoarthritis and
disc degeneration does not interfere with secretion but instead with extracellular assembly of matrix structures. In this review we summarize such information on matrilin structure and function that we believe is important for the understanding of extracellular matrix assembly and for deciphering pathophysiological mechanisms in diseases causing skeletal malformations or cartilage degeneration.