Fig. 10: Molecular basis of methuosis.

This image depicts the working model of methuosis. Methuosis is initiated by prolonged high-level expression of RAS (G12V) and chronic activation of Rac1, which leads to enhanced macropinocytic activity. Moreover, this mechanism hampers macropinosome recycling by lowering the active Arf6 pool. Nascent macropinosomes, which are created from lamellipodial membrane projections, penetrate the cell and merge to form large fluid-filled vacuoles that, in contrast to typical macropinosomes, cannot be recycled. These vacuoles grow rapidly, resulting in a stable population with certain late endosomal features (Rab7 and LAMP1).