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Vol. 17, Issue 6, 2581-2591, June 2006
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*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; and Institute of Molecular Biotechnology, Austrian Academy of Sciences, A-1030 Vienna, Austria
Submitted November 30, 2005;
Revised March 6, 2006;
Accepted March 27, 2006
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 such as 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 Nck-associated protein 1 (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 suppressor of cAMP receptor (scar) 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.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Theresia E.B. Stradal ( theresia.stradal{at}gbf.de) or Klemens Rottner ( klemens.rottner{at}gbf.de)
Abbreviations used: AlF4–, aluminum fluoride; Nap1, Nck-associated protein 1; Sra-1, Specifically Rac-associated protein 1; WT, wild type.
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