Diverse biological functions of extracellular collagen processing enzymes

Abstract

Collagens are abundant proteins in higher organisms, and are formed by a complex biosynthetic pathway involving intracellular and extracellular post-translational modifications. Starting from simple soluble precursors, this interesting pathway produces insoluble functional fibrillar and non-fibrillar elements of the extracellular matrix. The present review highlights recent progress and new insights into biological regulation of extracellular procollagen processing, and some novel functions of byproducts of these extracellular enzymatic transformations. These findings underscore the notion that released propeptides and other proteolytic products of extracellular matrix proteins have important biological functions, and that structural proteins are multifunctional. An emerging concept is that a dynamic interplay exists between extracellular products and byproducts with cells that helps to maintain normal cellular phenotypes and tissue integrity.

Figure 1

Relationship between collagen mRNA levels and cell layer collagen protein accumulation in differentiating osteoblasts. MC3T3-E1 pre-osteoblasts were cultured in differentiation medium [Hong et al., 2004], and RNA isolated at intervals. Cell layer collagen based on cell layer hydroxyproline measurements were determined from separate cultures grown at the same time. ▪, α 1-type I collagen mRNA levels determined by Northern blotting and densitometry normalized to 18S rRNA, ▴, cell layer collagen based on hydroxyproline measurements as described [Hong et al., 2004].