Fuel-injected cell motility

Abstract

Crawling cells use actin polymerization to generate a protrusive force at the front of the cell. Thus, motility requires a steady supply of actin monomers – the ‘fuel’ for cell locomotion. Peckham et al. 1xSpecific changes to the mechanism of cell locomotion induced by overexpression of β-actin. Peckham, M. et al. J. Cell Sci. 2001; 114: 1367–1377PubMedSee all References1 reasoned that overexpressing β-actin (the isoform most heavily implicated in cell motility) would be the equivalent of upgrading the family car to one with a bigger engine, increasing speed by increasing the actin ‘fuel supply’ at the leading edge. Sure enough, increasing β-actin levels in myoblasts by around 60% led to a doubling of cell speed. At the same time, protrusive and retractive activity increased, suggesting that actin dynamics at the periphery were enhanced by the greater availability of β-actin.So far, so good. Everything fits the ‘fuel supply’ model. The trouble comes when one delves a little deeper. The first surprise is that BDM (butanedione monoxime), an inhibitor of myosin motor proteins, reduces back to control levels the movement of cells overexpressing β-actin. Myosin inhibition does not abolish normal cell crawling as this event is driven by actin polymerization rather than actomyosin contraction. Thus, the additional motility induced by overexpressing β-actin appears to be driven by a myosin-dependent mechanism, unlike the normal motion of crawling cells. Even more surprising is the observation that overexpressing a mutated β-actin that is defective in its ability to polymerize also increases cell speed. Again, this increase can be eliminated with BDM treatment.In other words, the increase in speed induced by overexpressing β-actin does not result from a simple acceleration of the normal cell-motility engine. Instead, the authors propose a model in which increased actin expression enhances fluid-driven protrusion. Contraction at the rear of the cell triggers a cytoplasmic ‘wave’ that sweeps through the cell and pushes the membrane forwards at the leading edge. This suggestion of a fundamentally different locomotive mechanism is a fascinating one. Perhaps the family car hasn't had an upgrade after all – it's been fitted with a booster engine instead.