1. Initiation and Nucleation

Filopodia

Step 1. Initiation and Nucleation

The nucleation and/or branching of new actin filaments is critical for filopodia formation. Most G-actin-ATP polymerization occurs at the barbed end of an actin filament and is controlled by both the accessibility of these barbed ends and filament stability. Filopodia are more likely to grow from actin polymerization at local sites (e.g. formin-mediated) than from bundling of filaments initiated by the Arp2/3 complex [1].

Although non-muscle cells have a high concentration of G-actin-ATP (~100 μM) [2], pure G-actin monomers fail to nucleate new actin filaments efficiently due to the instability of actin oligomers. Additional factors are therefore required, which bind monomeric actin and modulate its polymerization properties. Among the most widely studied proteins that perform this task are the formins. The Arp2/3 complex has also been found to be critical for filopodia initiation [3], although this complex is more commonly associated with lamellipodia formation.

Following nucleation of the required components, initiation commences and involves the formation of a protrusion of at least 1 µm in length. The lifespan of a filopodium is relatively long and as such the frequency of initiation is comparatively low [3, 4].

A detailed description of Formin mediated nucleation, and the Arp2/3 complex-mediated nucleation can be found under Functional Modules.


Figure: Accessory proteins nucleate actin filaments. A. NPFs (e.g. WASp; Scar) bring together the Arp2/3 complex and actin monomers to nucleate new actin filaments and to form new branches from the side of pre-existing filaments. Arp2/3 complex remains at the minus end of the filament. B. Formin cooperates with profilin to nucleate new actin filaments. Formin remains at the plus end of the filament.

References

  1. Brill-Karniely Y., Ideses Y., Bernheim-Groswasser A. & Ben-Shaul A. From branched networks of actin filaments to bundles. Chemphyschem 2009; 10(16):2818-27. [PMID: 19847840]
  2. Rosenblatt J., Peluso P. & Mitchison TJ. The bulk of unpolymerized actin in Xenopus egg extracts is ATP-bound. Mol. Biol. Cell 1995; 6(2):227-36. [PMID: 7787248]
  3. Korobova F. & Svitkina T. Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol. Biol. Cell 2008; 19(4):1561-74. [PMID: 18256280]
  4. Dailey ME. & Smith SJ. The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 1996; 16(9):2983-94. [PMID: 8622128]
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Subpages (1): Figure: Accessory proteins nucleate actin filaments.
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