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A more recent version of this article appeared on June 1, 2006 Originally published as MBC in Press, 10.1091/mbc.E05-11-1088 on April 12, 2006
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Submitted on November 30, 2005
Revised on March 6, 2006
Accepted on March 27, 2006
*Signalling and Motility Group, ||Cytoskeleton Dynamics Group, and Department of Cell Biology, German Research Centre for Biotechnology, D-38124 Braunschweig, Germany; Institute of Biophysical Chemistry, Hannover Medical School, D-30623 Hannover, Germany; Institute of Molecular Biotechnology, Austrian Academy of Sciences, A-1030 Vienna, Austria
Monitoring Editor: Mark Ginsberg
Cell migration is initiated by plasma membrane protrusions, in the form of lamellipodia and filopodia. The latter rod-like projections may exert sensory functions and are found in organisms as distant in evolution as mammals and amoeba like Dictyostelium discoideum. In mammals, lamellipodia protrusion downstream of the small GTPase Rac1 requires a multimeric protein assembly, the WAVE-complex, which activates Arp2/3-mediated actin filament nucleation and actin network assembly. A current model of filopodia formation postulates that these structures arise from a dendritic network of lamellipodial actin filaments by selective elongation and bundling. Here we have analyzed filopodia formation in mammalian cells abrogated in expression of essential components of the lamellipodial actin polymerization machinery. Cells depleted of the WAVE-complex component Nap1 and, in consequence, of lamellipodia, exhibited normal filopodia protrusion. Likewise, the Arp2/3-complex, which is essential for lamellipodia protrusion, is dispensable for filopodia formation. Moreover, genetic disruption of nap1 or the WAVE-orthologue scar (suppressor of cAMP receptor) in Dictyostelium was also ineffective in preventing filopodia protrusion. These data suggest that the molecular mechanism of filopodia formation is conserved throughout evolution from Dictyostelium to mammals and show that lamellipodia and filopodia formation are functionally separable.
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