The study of intermediate filament (IF) post-translational modifications will constitute a major effort in the next grant period. IF proteins have provided a valuable tool for the purpose of cell identification due to their specificity for the main tissues forming the body (epithelia, mesenchyma, muscle, glia and neurons). However, the IF function still remain elusive and it is hoped that a study of post-translational modifications may provide some clues in this respect. The hypothesis is that these modifications may account for structural maturation by stabilizing the final shape of glia and neurons, including their processes. The study of hyaluronate-binding proteins in mature and immature CNS is the other major goal of this project. The remarkable transition from fibroblast-type IF (vimentin) to astrocyte-specific IF (GFA protein) occurring at the time of glial differentiation, suggested that immature glia display mesenchymal properties relevant to morphogenesis such as the production of an extracellular matrix playing a role in cell migration and axonal growth, and that the loss of these properties following differentiation may account for the lack of regeneration in mature spinal cord. Preliminary observations are consistent with this hypothesis. We have identified in mature CNS a brain-specific hyaluronate-binding protein produced by white matter (but not gray matter) astrocytes. Conversely, other hyaluronate-binding fractions co-localized in brain and mesenchyma during embryonal development.
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