Recent advances in large-scale screening approaches have led to the identification and characterization of the first chemical inhibitor of the large GTPase dynamin, an essential factor in fission of clathrin/AP-2-coated vesicles (Macia et al. 2006). Dynasore selectively and dose-dependently inhibits the GTPase activity of dynamins 1 and 2, and at higher doses presumably other dynamin family members. Dynasore-mediated blockade of clathrin-coated vesicle fission takes place within seconds and results in the accumulation of U-shaped, half-formed pits, as well as O-shaped intermediates stalled at the fission stage.

Based on its mechanism of action, dynasore acts as an inhibitor of all endocytic pathways known to be dependent on dynamin-mediated fission. These include, besides clathrin/AP-2-mediated endocytosis, fission of TGN-derived vesicles (McNiven 1998), caveolar endocytosis (Henley et al. 1998), podosome (Ochoa et al. 2000) and centrosome function (Thompson et al. 2004), and cell migration (Macia et al. 2006).

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