Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions

Abstract

Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this "core matrisome" comprises 300 proteins. In addition there are large numbers of ECMmodifying enzymes, ECM-binding growth factors, and other ECM-associated proteins. These different categories of ECM and ECM-associated proteins cooperate to assemble and remodel extracellular matrices and bind to cells through ECM receptors. Together with receptors for ECM-bound growth factors, they provide multiple inputs into cells to control survival, proliferation, differentiation, shape, polarity, and motility of cells. The evolution of ECM proteins was key in the transition to multicellularity, the arrangement of cells into tissue layers, and the elaboration of novel structures during vertebrate evolution. This key role of ECM is reflected in the diversity of ECM proteins and the modular domain structures of ECM proteins both allow their multiple interactions and, during evolution, development of novel protein architectures.

Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland

“…In its absence, expression of genes encoding core components of the ECM, ECM-associated signaling factors, and remodeling molecules are changed, suggesting that alterations in ECM function might underlie the observed phenotypes. In addition, integrin β1 initiates self-assembly of secreted FN dimers into a multimeric fibrillar matrix that subsequently affects formation of collagen fibrils (8). Ultimately, changes in the deposition and assembly of the ECM in the absence of epithelial integrin β1 may have altered its ability to provide structural support, and to function as a scaffold that binds and presents secreted growth factors to vascular cells (8).…”

“…In the ECM category, expression of the core matrisome components fibronectin (FN), six of 28 collagens, and laminin C1 were significantly altered (8) (Fig. 5C).…”

“…In turn, integrin binding to ECM affects deposition, organization, and remodeling of individual ECM components into functional supramolecular structures (8). Integrin β1 pairs with twelve separate α-chains to form the largest integrin subfamily, and its role in vascular development has been the subject of significant investigation.…”

Lung Extracellular Matrix and Fibroblast Function

“…The term "matrisome" has been introduced to describe the various fibrillar proteins, glycoproteins, proteoglycans, and their associated modifying molecules (e.g., metalloproteases, matricellular proteins) that compose the ECM of tissues (2). Recently, the matrisome of both rodent (3) and human lungs (4) has been characterized.…”

Expanding Proteostasis by Membrane Trafficking Networks

“…In eukaryotic cells, glycan management was expanded significantly by the invention of the TPN (Varki 2011). O-linked glycans, such as those found contributing to the highly abundant extracellular glycoproteins such as mucins (Thornton et al 2008) and proteoglycans (Hynes and Naba 2012), are particularly interesting examples of the use of the Anfinsen compartment strategy to confer new structural, functional, and solubility properties to a polypeptide chain sequence, modifications that are crucial for multicellular, higher Eukarya function. On the other hand, the management of proteins containing N-linked glycans starts in the ER through the activity of the evolutionarily conserved dolichol-linked glycosylation pathway involving the PN-folding components such calnexin, BiP, protein disulfide isomerases, and ER-associated degradation (ERAD) pathways (Ellgaard and Helenius 2003;Sifers 2010).…”