Abstract:
Fibronectin (FN) extracellular matrix contributes to multiple cellular processes as an adhesive framework and a source of environmental signals. FN functions primarily from within a fibrillar network. Its assembly into fibrils is mediated by interactions with integrin receptors and is facilitated by sulfation of the syndecan-2 receptor. Receptor binding induces domain-specific conformational changes that promote assembly. Fluorescence resonance energy transfer (FRET) analyses show that III1-2, a domain that is essential for formation of stable detergent-insoluble fibrils, undergoes conformational changes that stimulate FN-FN interactions. Additional regions of FN that enhance fibril stability are being identified using proteomic analysis of detergent-insoluble fibrils. Assembled FN matrix supports cell movements in development and disease. Cell interactions with FN matrix are modulated by the presence of other matrix proteins (such as tenascin-C and fibulin-1), by mechanical forces, and by changes in FN expression or deposition. For example, embryonic stem (ES) cells require adhesion to intermediate levels of FN matrix in order to undergo self-renewal. Knockdown of FN expression in ES cells or increased levels of FN substrate induce ES cell differentiation. Thus, the balance of cell-FN interactions plays important roles in FN fibril assembly and in controlling cell signaling and cell fate decisions.
Faculty Host: Thom Barker, 404.385.5039
