Targeting the actin-binding protein VASP to late endosomes induces the formation of giant actin aggregates.

In vitro, the vasodilator-stimulated phosphoprotein (VASP) acts as a regulator of actin filament assembly in many ways. In cells it localizes to sites where actin is rapidly polymerized such as filopodia, lamellipodia, and focal adhesions. We have mistargeted VASP to the surface of the late endosome in Dictyostelium cells thereby inducing the formation of a dense actin aggregate which sequesters various actin-binding proteins and endosomal components. Depletion of these proteins from the cytoplasm leads to phenotypes mimicking the corresponding knockout cells. Some properties of the actin aggregate are reminiscent of Hirano bodies that are often observed in nerve tissue from patients suffering from neurodegenerative diseases, opening the possibility that protein sequestration contributes to neuronal malfunction.