Résumé :
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Communication n° 100. The synemin gene belongs to the intermediate filament family, encoding proteins which confer resistance to mechanical stress and modulate cell shape. Different isoforms of synemin are produced by alternative splicing of the pre-mRNA and are under strong differential regulation during development. The isoforms differ from each other by the length of their C-terminal tail domain outside of the IF rod domain similar in all IF members. The synthesis of H/M isoforms starts in the embryo, whereas the synemin L isoform is present in adult muscles. The H/M isoforms are bound to desmin or vimentin in the muscle cells. We also show that synemin colocalizes with desmin aggregates in human skeletal muscle from patients with DRM. In the nervous system, the larger isoforms are detected as soon as 13 days in glial cells of mouse embryos, whereas the smaller isoform appears after birth, exclusively in neurons. In the brain cortex and hippocampus, and in the granular layer of the cerebellum as well as in motoneurons. The small neuronal synemin isoform is associated with neuronal markers. In glial cells, the large synemin isoforms are colocalized either with the GFAP or the vimentin networks. Under tissue fractionation and purification of IF, heavy synemin isoforms are found associated with GFAP, while the small isoform is found with a subpopulation of neurofilament polymers that is associated with the membranous compartment. These data demonstrate for the first time the selective expression of distinct isoforms of an IF specie, resulting from the alternative splicing of a single pre- mRNA, in distinct cell types within the same tissue, in which these isoforms are associated with the major IF network of these cells. From these findings, the three synemin isoformes differ in the sequences of their tail domains as well as in their developmental patterns suggests that they fulfill different functions.
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