Regulation of cell proliferation by the actin cytoskeleton

The actin cytoskeleton has long been known to be a key regulator of cell proliferation linking biochemical sensing of the environment with cell cycle progression. However, analysis of the mechanism responsible for this regulation has been hindered by the lack of tools to manipulate the actin cytoskeleton, short of using global actin inhibitors. We have discovered that the actin cytoskeleton is composed of multiple, functionally distinct, populations of actin filaments, each containing different isoforms of the actin filament associated protein, tropomyosin (Tm). This provides a mechanism to account for the functional specialisation of actin filaments and most importantly a strategy to functionally dissect these different actin filaments by manipulating the levels of the different Tm isoforms. We have made the novel observation that actin filaments containing the Tm isoform Tm5NM1 regulate cell proliferation. This project aims to dissect the molecular mechanism(s) by which Tm5NM1-containing actin filaments regulate cell proliferation.