Steps in Filopodia Formation and Movement

Steps in Filopodia Formation and Movement: Overview

Filopodia are dynamic structures whose initiation and elongation are precisely regulated by the rate of actin filament assembly, convergence and cross-linking. Any change in the frequency of initiation or the balance of extension versus retraction of actin filaments can result in the gain or loss of filopodia.

Filopodia protrude from cells by a treadmilling mechanism of actin elongation [1]. According to this model, actin filaments elongate at their barbed ends and release subunits from their pointed ends. The influence of the substrate and growth factors upon filopodial protrusion, adhesion, and growth cone guidance were described in detail in the early 1980s [2]. Actin filaments in filopodia are unbranched [3], suggesting that assembly occurs by elongation and not by branched nucleation. Observations of filopodial formation revealed that actin assembled at filopodial tips, moved backward, and dissipated at the rear [3]. A complete model for how a filopodium is formed has recently been reviewed [4].

Figure: Dynamic behaviors of filopodia. Here we outline nine behaviors (1-9) and then consider underlying functional modules (A-G) that must be involved in the observed behaviors. Multiple protein modules are needed for the sustained function of each of these observable behaviors. Double-sided arrows symbolize the ability of a filopodium to oscillate between different states.

Figure: Steps in filopodium formation. Actin filament assembly can be initiated by uncapping pre-formed actin filaments or by de novo formation (which includes both formin- and Arp2/3-mediated [not shown] nucleation). The force produced by actin assembly at the barbed end of actin filaments drives membrane protrusion. Numerous proteins (including IRSp53, Ena/VASP proteins, WASp/Scar proteins) cooperate to promote actin-assembly and enhance bundling of actin filaments by fascin. When the barbed end of the filament is capped, this stops filament assembly and protrusion; continued retrograde movement of the filaments results in retraction of the filopodium. (Figure adapted from [5]).

References

  1. Small JV. Lamellipodia architecture: actin filament turnover and the lateral flow of actin filaments during motility. Semin. Cell Biol. 1994; 5(3):157-63. [PMID: 7919229]
  2. Svitkina TM. & Borisy GG. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 1999; 145(5):1009-26. [PMID: 10352018]
  3. Mallavarapu A. & Mitchison T. Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J. Cell Biol. 1999; 146(5):1097-106. [PMID: 10477762]
  4. Ahmed S., Goh WI. & Bu W. I-BAR domains, IRSp53 and filopodium formation. Semin. Cell Dev. Biol. 2010; 21(4):350-6. [PMID: 19913105]
  5. Faix J. & Rottner K. The making of filopodia. Curr. Opin. Cell Biol. 2006; 18(1):18-25. [PMID: 16337369]
Back to top