Extracellular Matrix and Cell Signaling Transduction

Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans.

The diverse array of ECM proteins not only support the physical structure of the cell but also various biological functions, largely through their ability to bind multiple interacting partners such as other ECM proteins, growth factors, signal receptors and the adhesion molecules, which is mediated by the multiple, specific domains present within each protein.

HSPGs are proteoglycans found in extracellular matrix (ECM) with multiple heparan sulphate (HS) side chains covalently coupled to the core protein. HSPGs present in the matrix include perlecan, agrin, collagen type XI, syndecans and glypicans. The perlecan, agrin and collagens are actively secreted into the ECM, while the syndecans and glypicans are cleaved from the cell surface by proteases and phospholipases respectively.

Cells respond to the mechanical and biochemical changes in extracellular matrix (ECM) through the crosstalk between integrins and the actin cytoskeleton.

Integrins are heterodimeric transmembrane receptors composed of eighteen alpha subunits and eight beta subunits that can be non-covalently assembled into 24 combinations. The integrin dimers bind to an array of different ECM molecules with overlapping binding affinities.

The specific integrin expression patterns by a cell dictate which ECM substrate the cell can bind and the composition of integrin adhesomes determines the downstream signalling events, thus the eventual cell behaviour and fate.

Extracellular matrix (ECM) proteins play crucial and complex roles during cell surface receptor signalling.

First of all, ECM serves as a reservoir for growth factors. ECM-bound growth factors could be released locally and bind to their canonical receptors. Many ECM proteins have binding sites for both cell adhesion and growth factors, allowing local concentration of the growth factors near to their cell surface receptors and cell adhesion sites.

This localisation of growth factors, and thus their signalling, by the ECM probably contributes to the establishment of gradients of the soluble, diffusible growth factor morphogens, which play vital roles in patterning indevelopmental processes. Such examples include fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), both of which bind to HSPG and can be cleaved off from the glycosaminoglycan components of HSPG by the enzyme heparanase and released as soluble ligands.

Extracellular matrix (ECM) is a generic term encompassing mixtures of polysaccharides and proteins, including collagens, fibronectins, laminins, and proteoglycans, all secreted by the cell.

Extracellular matrix (ECM) provides a route for cell migrations, and molecules in the matrix activate classic signal-transduction pathways that induce cell growth, proliferation, and gene expression. These many effects of the matrix involve membrane-bound CAMs that bind directly to components of the ECM and the cytoskeleton.

Cells attach to the underlying extracellular matrix through two types of integrin-dependent junctions: focal adhesions, which attach the actin cytoskeleton to fibers of fibronectin, and hemidesmosomes, which connect intermediate filaments to basal laminae.

Cell Signaling Transduction