New insights into roles of intermediate filament phosphorylation and progeria pathogenesis

Intermediate filaments (IFs) form one of the major cytoskeletal systems in the cytoplasm or beneath the nuclear membrane. Because of their insoluble nature, cellular IFs had been considered to be stable for a long time. The discovery that a purified protein kinase phosphorylated a purified IF protein and in turn induced the disassembly of IF structure in vitro led to the novel concept of dynamic IF regulation. Since then, a variety of protein kinases have been identified to phosphorylate IF proteins such as vimentin in a spatiotemporal regulated manner. A series of studies using cultured cells have demonstrated that preventing IF phosphorylation during mitosis inhibits cytokinesis by the retention of an IF bridge-like structure (IF-bridge) connecting the two daughter cells. Knock-in mice expressing phosphodeficient vimentin variants developed binucleation/aneuploidy in lens epithelial cells, which promoted microophthalmia and lens cataract. Therefore, mitotic phosphorylation of vimentin is of great importance in the completion of cytokinesis, the impairment of which promotes chromosomal instability and premature aging.