Transmembrane and multiplexin collagens in development and pathobiology

At its best, it is exhilarating to make unexpected discoveries when addressing carefully formed scientific hypotheses. This review depicts my scientific journey in the field of extracellular matrix biology, and more specifically in collagen research, starting in 1978 and continuing with exciting findings up to the present day. While recounting my early work on the enzymes of collagen biosynthesis, the focus will be on our discoveries of new types of nonfibrillar collagen: type XIII collagen, belonging to the MACIT subgroup among the collagen family of proteins, and types XV and XVIII collagens, constituting the multiplexin subgroup. We have investigated these collagens through molecular biological approaches in order to define their primary structures, and through biochemical and cell biological work to understand their special molecular properties. Furthermore, the generation of many mouse models has led us to exciting studies of the roles of these collagens in adipose tissue, bone, eye, heart, kidney, liver, peripheral nerves, skin, and cancer models, although it has of course also been rather daunting in terms of choosing the correct approach for each tissue. The work on animal models has nevertheless resulted in a broad understanding of the in vivo significance of these collagens, forming a fruitful basis for studying their relevance to human diseases, including malignant processes. Our conclusions have been that these collagens can contribute to the stability of the extracellular matrix and tissue structures, e.g., the basement membrane and the adjacent fibrillar matrix in the case of the multiplexins and the motor synapse in the case of the MACIT type XIII collagen, and more unexpectedly, that they possess major roles as extrinsic regulators of the fates and functions of cells.