Structural and Functional Properties of CCN Proteins

The CCN family currently comprises six members (CCN1–6) that regulate diverse cell functions, including mitogenesis, adhesion, apoptosis, extracellular matrix (ECM) production, growth arrest, and migration. These properties can result in a multiplicity of effects during development, differentiation, wound healing, and disease states, such as tumorigenesis and fibrosis. CCN proteins have emerged as major regulators of chondrogenesis, angiogenesis, and fibrogenesis. CCN proteins are mosaic in nature and consist of up to four structurally conserved modules, at least two of which are involved in binding to cell surfaces via molecules that include integrins, heparan sulfate proteoglycans, and low-density lipoprotein receptor-related protein. CCN proteins use integrins as signal transducing receptors to regulate context-dependent responses in individual cell types. The involvement of integrins in mediating CCN signaling allows for considerable plasticity in response because some effects are specific for certain integrin subtypes and integrin signaling is coordinated with other signaling pathways in the cell. In addition to their own biological properties, CCN proteins regulate the functions of other bioactive molecules (e.g., growth factors) via direct binding interactions. CCN molecules demonstrate complex multifaceted modes of action and regulation and have emerged as important matricellular regulators of cell function.