Filopodium Assembly

Steps in Filopodia Formation and Function[Edit]

Filopodia are dynamic structures that are primarily composed of F-actin bundles and whose initiation and elongation are precisely regulated by the rate of actin filament assembly, convergence and cross-linking. 
Figure 1. Dynamic behaviors of filopodia: Filopodia undergo 9 distinct steps in their formation. Double-sided arrows symbolize the ability of a filopodium to oscillate between different states.
The actin treadmilling mechanism of elongation is essential in protrusion [1] and 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. Filopodial actin filaments are unbranched [2], and observations of filopodial formation have revealed that actin assembles at the filopodial tips, moves backwards, and dissipates at the rear [3]. A complete model for how a filopodium is formed has recently been reviewed [2].

Actin nucleation initates filopodium formation[Edit]

The first step in the formation of a filopodium is the nucleation of actin filaments from G-actin monomers. This is facilitated by various proteins known as nucleators, and may occur via the 'tip nucleation model' or the 'convergent nucleation model'. In the former model, members of the formin family of proteins cluster at the plasma membrane and initiate the nucleation of actin filaments; in the latter model Arp2/3 complex nucleated branches continually develop from the actin filament network located at the leading edge of the lamellipodia.

Current research into these models suggests that both remain plausible mechanisms for actin filament nucleation and filopodia initiation in vivo, however only the "convergent elongation model" is supported with direct experimental evidence. Much of this evidence is based on the effect of modulating activators or regulators of the Arp2/3 complex, although some findings are directly attributed to the expression and function of the Arp2/3 complex itself.

Figure 2. 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.
It has been shown, for example, that Arp2/3 knockdown in cultured neurons [4] as well as loss-of-function mutations in C. elegens [5] and cultured Drosophila neurons [6], leads to a disruption in filopodia initiation and subsequently a decrease in the number of filopodia. Modulation of nucleation-promoting factors (NPFs) that act directly on Arp2/3 have also been shown to influence filopodia initiation. In one example, targeted depletion of SCAR by RNA interference reportedly inhibited both lamellipodia and filopodia formation in Drosophila where as depletion of N-WASP did not [7]. It has also been reported that although N-WASP was not essential for filopodia formation, its activation lead to an increased number of filopodia, again implicating the Arp2/3 complex in filopodia initiation. This was observed in COS-7 cells co-expressing N-WASP with a Myc-tagged Cdc42 mutant (an activator of N-WASP) where 'extremely long' microspikes were described in half the anti-Myc positive cells [8]. Similarly, expression of a mutant form of WASP (Y291E), which mimics phosphorylated Tyr291, was shown to induce filopodia in macrophages more effectively than wildtype WASP [9]. The same study also reported that filopodia formation was induced in macrophages as a result of WASP over-expression, and noted that WASP co-localized with F-actin at the filopodia base [9]. More recently, Robo4 was shown to induce filopodia formation in endothelial cells. This role was attributed to its activation of NPFs such as WASP, which in turn activates the Arp2/3 complex. It was also proposed that Robo4 may act as a molecular scaffold for the recruitment of of proteins that mediate actin nucleation [10] . Additional experimental evidence supporting the "convergent elongation model" has been summarized extensively [11].

Cross-linking and extension of actin filaments[Edit]

Once nucleation has taken place, actin filaments begin to extend. This process is primarily facilitated by members of the formin family of proteins, however numerous other proteins also play important roles. In the 'convergent elongation model' filament barbed ends are locally associated with each other and must be protected from capping in order for extension to occur [12].
Figure 3. Steps in filopodium formation: 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 Faix J and Rottner K, 2006)
This protection is provided by the activity of proteins such as the Ena/VASP family of proteins which is delivered to the filopodia tip by myosin X [13]. Here, Ena/VASP enhances filament polymerization, and promotes F-actin bundling, thereby stimulating filopodial protrusion [12, 14, 15, 16, 17].

Actin filaments in filopodia are unbranched [18], indicating filaments elongate primarily through the activity of formins. Following the rapid polymeriztaion facilitated by formins, a steady state mechanism that is common to many actin based structures will maintain filament length. This is known as actin treadmilling [1] and is described in greater detail in the functional module; actin filament polymerization.

As actin filaments extend, force is exerted on the cellular membrane, leading filopodia protrusion. For efficient protrusion, membrane curvature rigidity must be overcome. This is aided by actin filament cross-linking, which gives the structure the strength required to push against the compressive force of the plasma membrane [17, 19]. In nerve growth cones, more than 15 parallel filaments may be bundled together by crosslinking [20]. Bundle stiffness increases with the number of bundled filaments and so contributes to the overall length of the filopodium [17]. Filament bundling results from crosslinking proteins, many of which co-localize at the base of filopodia and work in concert to produce crosslinked filaments [21]. Examples include α-actinin and fascin. The filamin family of proteins are also crucial actin crosslinking and scaffolding proteins and bind to both actin and a number of signaling molecules, including Rho GTPases. Crosslinking also increases the ATPase activity of myosins and increases the tension on filaments [22].

As well as mediating cargo transport along actin filament bundles, recent studies have implicated myosin-X as integral to the initiation of filopodia and the elongation of long filopodia. This has been attributed to a mechanism of myosin-X that promotes actin filament bundling, similar to cross-linking.

Studying the localization and motility of single myosin-X molecules using TIRF microscopy, Watanabe et al, hypothesized that binding of cargo, and the preceding dimerization of myosin-X monomers at the cell periphery is important for filopodia initiation as it promotes actin filament bundling [23]. This was proposed to occur in a similar manner to regular crosslinking. Previous reports had indicated that even without the cargo-binding FERM domain, lateral movement of myosin-X along the leading edge of lamellipodia promoted actin reorganization and through its motor activity, filopodia initiation. In this case the length of the head and neck domain of myosin-X was proposed to be important for initiation. In the study by Watanbe et al a rapid increase in the rate of recruitment and assembly of myosin-X at filopodia initiation sites moments before protrusion commenced was observed and again this was shown to be independent of the presence of the FERM domain.

After removing the FERM domain from myosin-X (using a FERM domain-truncated construct called M10-ΔFERM) the protein was still able to walk along actin filament bundles and continued to localize at both the leading edge and filopodia tip. Significant changes to the length and stability of the growing filopodia were however noted. Not only were filopodia significantly shorter and more unstable, as previously reported [24, 25], but the phased-extension mechanism of elongation observed when complete myosin-X was present, did not occur.

Although it was noted that without the FERM domain the transport of essential cargo to the tips of the filopodia would be insufficient to permit continued elongation, it was also proposed that through FERM-β-integrin interactions at the tips of filopodia (when filopodia are attached to substrates via focal adhesion sites), myosin-X may also possess adhesive qualities. In this hypothesis, as filopodia enter the retraction phase and actin filaments move back towards the cell body by retrograde flow, myosin-X remains at the tips of filopodia together with the adhesion complex. Upon shrinkage of the tips, the protein will rebind to actin filament bundles and allow a new phase of extension to begin from adhesion sites. This mechanism of phased-extension is supported by observations that without the FERM domain myosin-X diffuses back into the cell body during the retraction phase whilst intact myosin-X remains at the tips [23].

The rate of filopodia extension[Edit]

The extension rate of a filopodium will differ depending on the cell type (table 1). In each case however, this rate is controlled by the availability of G-actin-ATP, associated structural components and the energetics of membrane bending. The growth of long filopodia (>10 μm in length) requires the rapid transport of key materials towards the growing end [26] and this process is facilitated by the myosin motor proteins such as myosin X or IV using an ATP-dependent ‘walking’ mechanism. Although the extension of filopodia is often described in a highly ordered manner, and does rely on the defined movements of Myosin-X for component delivery to the filopodia tip, the contribution of random diffusion of components must also be considered. Stochastic simulation models were recently presented that describe such phenomena, where 'molecular noise' may influence concentration gradients of G-actin as well as efficacy of the machinery responsible for filopodia growth. 

One such study indicates that although the spatial distribution of static Myosin-X is universally consistent, and not altered by organelle length, the concentration of walking motors may vary. "Traffic jams" of myosin-X may occur for example at the base of the filopodia. Although logically this will impede progression of the proteins and their cargo down the filament, it was calculated that following a build up of G-actin at the blockage site, a concentration gradient is generated that enables its diffusion down the filopodia, (so long as the G-actin is not sequestered by the blocked motors) which subsequently sustains filopodia extension [27]. Similarly, the constant association and dissociation of capping protein at the barbed ends of actin filaments has been shown, also using stochastic simulations, to influence the dynamics of filopodia extension. In this case amplification of these regulatory proteins from initially low concentrations may trigger the fast retrograde flow of actin and induce repeated extension-retraction cycles that occur on a micro-meter scale. Compared to actin-only models, these dynamic cycles enable the growth of substantially longer filopodia [28].

Table: Filopodial Extension Rates
System Maximum Rate Reference
Mouse cortical neurons 500 nm/s Sheetz et al., 1992 [29]
NG108 30 nm/s Mallavarapu & Mitchison, 1999[3] 
Dictyostelium cells ~30 nm/s Schirenbeck et al., 2005 [30]
Helisomatrivolvis ~40 nm/s Tornieri et al., 2006 [31]
Dictyostelium cells 1000 nm/s Medalia et al., 2007 [32]
Chick DRG neurons 300 nm/s Constantino et al., 2008 [33]
Primary mesenchyme cells ~150 nm/s Miller et al., 1995 [34]

Lateral movement of filopodia[Edit]

Filopodia are motile structures, being able to extend, retract and move laterally as they sense their environment. Lateral movement is particularly important in allowing the structure to sense stimuli prior to its adhesion with another cell or substrate. 
Figure 4. Lateral movement of filopodia: The direction of cell movement in a migrating cell is primarily controlled by actin filament assembly at the leading edge. In the diagram above, increased actin polymerization at the side of the filopodium (yellow arrow) pushes the membrane forward and to the left (panel #1). The forces produced by actin polymerization against the actin bundles of a filopodium can lead to lateral movement (panels #2 & 3). Under the microscope, filopodia appear to cross-over one another as distinct units when they are separated within the three-dimensional framework of the cell (panels #4-6). When a laterally moving filopodium encounters another filopodium within the same three-dimensional space, the two filopodium can fuse to become one; this frequently increases the width and length of the resulting filopodium (panels #7 & 8).
Lateral movement may be a consequence of filopodial protrusions being tilted with respect to the retrograde flow of actin [1, 35]. This movement is inhibited once filopodia adhere to cells or substrates [36], however it is important to note that newly emerged filopodia seldom adhere to the substratum at their tips and are instead more likely to adhere at their bases [37].

Lateral movement and merging of filopodia may also stimulate further elongation of filopodia, suggesting that this may be an alternative method for promoting filopodial maturation and growth cone advancement on less adherent substrates [36].

Filopodia stasis[Edit]

Typically filopodia are quite dynamic and are constantly growing or retracting. Thus, periods of stasis are often short-lived and even adhesion of the filopodial tip to a substrate will not last long before the cell pulls on the site and recruits additional components or retracts, leaving behind a thin tube of membrane. There are several events that may promote stasis in retracting filopodia.

1) Ligand binding to filopodial receptors and subsequent adhesion of the ligand/receptor complex to actin bundles:
After a ligand binds to a receptor on the filopodium, lateral connections between the receptor and the actin bundle(s) prevent retrograde actin movement relative to the ligand. This inhibition converts the previous retrograde movement of the retracting filaments into tension on the bundles. This tension might influence polymerization and stability of actin filaments and/or myosin activity.

2) Ligand binding to filopodial receptors followed by uncapping of filament barbed ends:
Retracting filopodia become static when receptor binding leads to filament uncapping and rapid polymerization at the barbed end. The retraction force is converted to retrograde flux and the filament length remains constant.

3) Capping of unstable actin filaments [38]:
If retraction occurs by barbed end disassembly, capping of unstable filaments by an activated receptor will block retraction and induce stasis.

Filopodia adherence to the cell substrate[Edit]

A diverse array of cellular responses can result when a filopodium makes contact with a ligand or substrate. These responses are dependent on the coupling of membrane-bound proteins to the backward (retrograde) 
Figure 5. No adhesion to the substrate limits filopodial protrusion: A lack of adhesion (1a) causes actin treadmilling to be converted mainly into retrograde flow (1b).
flow of actin that drives filopodia elongation and motility. This contributes to larger processes such as cell pulling, which is needed for cell migration in wound healing, neurite growth [39], filopodia collapse and momentary stasis. These responses are influenced by the strength of the adhesion and it is known that contact differences between substrates or cell types influence the number of protruding filopodia [40].

Three distinct types of adhesions can be identified within filopodia. Adhesion components may be localized to the tips of filopodia or be actively transported down the bundled actin filaments by myosin proteins. Each adhesion may function independently or work in concert to produce the overall guidance response:

Tip adhesions

Figure 6. Adhesion influences filopodia protrusion: Adhesion acts like a "molecular grip" and influences the protrusion of filopodia (2a). Adhesion between membrane-anchored integrins and the extracellular substrate (e.g. fibronectin) causes clustering of focal adhesion components (represented by a hand,2b). Connections between the adhesions and the actin cytoskeleton converts the force generated by actin polymerization into protrusion(2c).
Filopodia on apposed cells interact directly through their tips [41] and/or 'slide' past each other (interdigitate) in order for adhesions to form (through cadherin-cadherin contact) between the tip of one filopodia and the cell membrane at the base of the adjacent filopodium [42]. Tip adhesions are likely to contain proteins that are found in nascent focal complexes [43, 44, 45]. Depending on the type of substrate, and strength of the adhesion, the resulting response may differ. In filopodia extending from neuronal growth cones, signals originating from tip adhesions can result in the formation of shaft adhesions, veil advance, and ultimately, growth cone movement [8].

Shaft adhesions

A single filopodium can have both non-adherent and adherent regions along the shaft. Shaft adhesions develop de novo along the filopodium and do not represent former tip adhesions [8]. Growth cone veils advance easily on non-adherent regions and cease movement as they encounter stable shaft adhesions; lateral mobility, veil advance and the merging of filopodia are also regulated by shaft adhesions [8].

Basal adhesions

Figure 7. Types of adhesions found in filopodia.: Three distinct adhesion types are found in filopodia: tip adhesions serve as guidance cues, shaft adhesions help control lamellipodial advance, and basal adhesions assist with filopodia emergence and are involved with components linking the cell to the substratum.
Basal adhesions play a specific role in filopodia initiation and are found in ~98% of all filopodia, where they anchor the filopodial base that usually remains immobile despite considerable flexibility in the shaft [36]. These are stable adhesions that contain a focal ring structure believed to convert tension forces into filopodia formation. Basal adhesions are stable and are formed before the filopodium emerges. This has been observed in growth cones where they remain in place as the growth cone advances [36].

Increasing the force on an adhesion, either by an external source or by increasing cellular contractility, strengthens and enlarges the adhesion [46]. Similarly, in basal adhesions of filopodia in neuronal growth cones, the size and stability of nascent adhesion increases in a maturation process that is reminiscent of the focal adhesions (FAs) found in non-neuronal cells [43, 44]. Though smaller than FAs, these adhesions share a number of signal components, pathways, and proteins leading to adhesion site formation and maturation [47, 45, 48].The structure of the growth cone adhesion site varies with the substrate [44] and adhesion directs growth cone navigation and movement (reviewed in [49, 50]).

Filopodia Pulling[Edit]

Although a reterograde motion of actin filaments is intrinsic in the formation of filopodia, the forces generated by actin treadmilling are too weak to facilitate the “pulling? mechanism required for rigidity sensing and other mechanosensing processes. This characteristic of filopodia is instead produced by the activity of myosin motor proteins such as Myosin II [51]. This process, as described in the Functional Module: ‘Microfilament Motor Activity’, is similar to that observed in the actin filament networks of the lamellipoda and lamella. Disassembly of actin bundles at the filopodial tip combined with the tension of the lipid bilayer also theoretically support the forces needed for pulling [52].

Figure 8. Filopodia can pull objects: After a filopodium binds to an object, retrograde actin movement and myosin motor activity provide the force(s) needed for pulling the object towards the cell body. Once pulling starts, the initial slow movement (#1) is followed by a burst of rapid movement (#2) that diminishes as the object reaches the cell body (#3) [53].
Filopodia pulling is important in a number of processes additional to mechanosensing. One example is in the immunological response to pathogens where immune cells such as macrophages will pull a pathogen toward the cell body for active uptake and processing [54]. In another example the filopodia of mature osteoclasts bind to extracellular substrates at their tips and transport the particles rearward by retraction for resorption to the cell body, leaving the cell body adhered to the substrate [55]. It has also been shown that matrix coated beads are pulled rearward by an active process rather than by diffusion after the beads bind to integrins [51, 26].

In each case the mechanism behind pulling remains the same. While the powerstroke of Myosin II essentially drives the movement of filaments, the pulling process occurs over three distinct stages, each defined by varying rates of retraction. These can be described using the process by which pathogens are pulled towards macrophage cell bodies as an example. Here, immediately following filopodial adhesion to a pathogen, a slow motion retraction of the filopodia commences. This is followed by a phase of rapid movement where the pathogen is pulled towards the cell. A final phase of slow retraction occurs, resulting in the pathogen being fixed to the cell surface. This final phase of retraction is also characterized by a thickening of the filopodial base which is necessary to build-up large retraction forces for internalization [52, 55]. Filopodial attachment to a surface (in addition to the ligand) produces counteracting adhesion forces which influence the retraction speed. In general, the rearward movement or ‘step size’ of a retracting filopodia decreases as the filopodia encounters a greater counteracting force [51]. Importantly, the mechanism may also be hijacked by a pathogen to ensure an efficient infection. This has been described for the Murine Leukemia Virus, amongst others [52]. In this case the virus binds to surface receptors at the tips of the filopodia and essentially rides the retracting actin filaments to entry points in the cell where it is internalized.

Filopodia Retraction and Collapse[Edit]

Binding of filopodia to certain ligands or substratum may hinder filament assembly, thereby leading to changes that promote retraction, collapse or growth cone turning [40, 56]. For example, substrate contacts with a repulsive signal on one side of a filopodium causes growth cone turning, while contact across the entire filopodial tip circumference causes complete filopodium collapse [40]. Normal retrograde flow of material continues under both circumstances and collapse is independent of the maintenance of growth cone protrusive activity [57]. Resorption and collapse are related processes and likely involve the same core proteins. .

Table: Filopodial Retraction Rates
System Maximum Rate References
Mouse cortical neurons; primary mesenchyme cells 400 nm/s  [2934]
NG108 15 nm/s  [3]
Mouse macrophage 600 nm/s [58]
Chick DRG neurons 200 nm/s  [33]

Figure 9. Model of filopodia collapse: In neuronal growth cones, filopodia protrusion stops when a repulsive signal binds to its receptor on the cell surface. Receptor-binding transiently inactivates Rac1 GTPase and prevents it from promoting actin assembly. Resumption of Rac1 activity coincides with filopodia collapse and is required for endocytosis of the collapsing plasma membrane and reorganization of F-actin [59]. RhoA and its effector, ROCK, are activated downstream of repulsive cues [60, 59, 61] and their activity has been implicated in reducing actin polymerization following treatment with repulsive signals [62].
Rapid collapse produces a large number of filopodial strands tightly connected to the substrate by long tethers. F-actin bundles [63] and monomeric actin [56] disappear from collapsing filopodia without a compensatory rise in F-actin at the growth cone center; this indicates a net loss of actin rather than a rearward translocation. Furthermore, active nucleation and protrusion of filopodia is still found in discrete areas of collapsing growth cones, which argues against sequesterization or modification of actin as the mechanism responsible for the loss of F-actin during the collapse [56].

A number of factors regulate collapse and retraction. For example, capping proteins promote filopodial retraction by shielding the barbed end of filaments from further assembly and elongation [64]. Inhibition of F-actin polymerization and protrusion during collapse are mediated by RhoA kinase activity [65]. Collapse may result from the exposure of a “naive? growth cone to a high concentration of a repellent followed by an overactive response [66]. The repulsive component appears to shut down the growth program and is therefore dominant over the growth-stimulating effects of adhesion molecules. In addition, the repellent also interferes with mechanisms that would normally result in filopodial retraction [40].

Growth Cone Collapse[Edit]

Growth cone collapse is a complex phenomenon involving numerous signal pathways including Rho-GTPases [67], ADF [68], and kinases [69, 70]. A model for filopodia collapse in growth cones was created using the guidance signal, semaphorin IIIA (SemaIIIA; collapsin-1). SemaIIIA causes termination of protrusive activity and growth cone collapse [71] through decreased phosphorylation of the ezrin–radixin–moesin (ERM) family of F-actin binding proteins [72]. Phosphorylation of ERM proteins activates the F-actin binding domain and regulates filopodia assembly/protrusion by linking filopodial membranes with F-actin (reviewed in [73]). Inactivation of the phosphoinositide 3-kinase (PI3K) signal pathway by SemaIIIA may also be linked to reduced ERM protein activity and growth cone collapse [72].


  1. Lamellipodia architecture: actin filament turnover and the lateral flow of actin filaments during motility. Semin. Cell Biol. 1994; 5(3). [PMID: 7919229]
  2. Ahmed S., Goh WI., Bu W. I-BAR domains, IRSp53 and filopodium formation. Semin. Cell Dev. Biol. 2010; 21(4). [PMID: 19913105]
  3. Mallavarapu A., Mitchison T. Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J. Cell Biol. 1999; 146(5). [PMID: 10477762]
  4. 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). [PMID: 18256280]
  5. Norris AD., Dyer JO., Lundquist EA. The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans. Neural Dev 2009; 4. [PMID: 19799769]
  6. Gonçalves-Pimentel C., Gombos R., Mihály J., Sánchez-Soriano N., Prokop A. Dissecting regulatory networks of filopodia formation in a Drosophila growth cone model. PLoS ONE 2011; 6(3). [PMID: 21464901]
  7. Biyasheva A., Svitkina T., Kunda P., Baum B., Borisy G. Cascade pathway of filopodia formation downstream of SCAR. J. Cell. Sci. 2004; 117(Pt 6). [PMID: 14762109]
  8. Miki H., Sasaki T., Takai Y., Takenawa T. Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Nature 1998; 391(6662). [PMID: 9422512]
  9. Cory GO., Garg R., Cramer R., Ridley AJ. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J. Biol. Chem. 2002; 277(47). [PMID: 12235133]
  10. Sheldon H., Andre M., Legg JA., Heal P., Herbert JM., Sainson R., Sharma AS., Kitajewski JK., Heath VL., Bicknell R. Active involvement of Robo1 and Robo4 in filopodia formation and endothelial cell motility mediated via WASP and other actin nucleation-promoting factors. FASEB J. 2009; 23(2). [PMID: 18948384]
  11. Yang C., Svitkina T. Filopodia initiation: focus on the Arp2/3 complex and formins. Cell Adh Migr undefined; 5(5). [PMID: 21975549]
  12. Svitkina TM., Bulanova EA., Chaga OY., Vignjevic DM., Kojima S., Vasiliev JM., Borisy GG. Mechanism of filopodia initiation by reorganization of a dendritic network. J. Cell Biol. 2003; 160(3). [PMID: 12566431]
  13. Tokuo H., Ikebe M. Myosin X transports Mena/VASP to the tip of filopodia. Biochem. Biophys. Res. Commun. 2004; 319(1). [PMID: 15158464]
  14. Schirenbeck A., Arasada R., Bretschneider T., Stradal TE., Schleicher M., Faix J. The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation. Proc. Natl. Acad. Sci. U.S.A. 2006; 103(20). [PMID: 16675552]
  15. Lebrand C., Dent EW., Strasser GA., Lanier LM., Krause M., Svitkina TM., Borisy GG., Gertler FB. Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1. Neuron 2004; 42(1). [PMID: 15066263]
  16. Han YH., Chung CY., Wessels D., Stephens S., Titus MA., Soll DR., Firtel RA. Requirement of a vasodilator-stimulated phosphoprotein family member for cell adhesion, the formation of filopodia, and chemotaxis in dictyostelium. J. Biol. Chem. 2002; 277(51). [PMID: 12388544]
  17. Mogilner A., Rubinstein B. The physics of filopodial protrusion. Biophys. J. 2005; 89(2). [PMID: 15879474]
  18. 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). [PMID: 10352018]
  19. Mogilner A., Oster G. Cell motility driven by actin polymerization. Biophys. J. 1996; 71(6). [PMID: 8968574]
  20. Lewis AK., Bridgman PC. Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity. J. Cell Biol. 1992; 119(5). [PMID: 1447299]
  21. Tseng Y., Kole TP., Lee JS., Fedorov E., Almo SC., Schafer BW., Wirtz D. How actin crosslinking and bundling proteins cooperate to generate an enhanced cell mechanical response. Biochem. Biophys. Res. Commun. 2005; 334(1). [PMID: 15992772]
  22. Coleman TR., Mooseker MS. Effects of actin filament cross-linking and filament length on actin-myosin interaction. J. Cell Biol. 1985; 101(5 Pt 1). [PMID: 2932451]
  23. Watanabe TM., Tokuo H., Gonda K., Higuchi H., Ikebe M. Myosin-X induces filopodia by multiple elongation mechanism. J. Biol. Chem. 2010; 285(25). [PMID: 20392702]
  24. Bohil AB., Robertson BW., Cheney RE. Myosin-X is a molecular motor that functions in filopodia formation. Proc. Natl. Acad. Sci. U.S.A. 2006; 103(33). [PMID: 16894163]
  25. Zhang H., Berg JS., Li Z., Wang Y., Lång P., Sousa AD., Bhaskar A., Cheney RE., Strömblad S. Myosin-X provides a motor-based link between integrins and the cytoskeleton. Nat. Cell Biol. 2004; 6(6). [PMID: 15156152]
  26. Schmidt CE., Dai J., Lauffenburger DA., Sheetz MP., Horwitz AF. Integrin-cytoskeletal interactions in neuronal growth cones. J. Neurosci. 1995; 15(5 Pt 1). [PMID: 7751919]
  27. Zhuravlev PI., Lan Y., Minakova MS., Papoian GA. Theory of active transport in filopodia and stereocilia. Proc. Natl. Acad. Sci. U.S.A. 2012; 109(27). [PMID: 22711803]
  28. Zhuravlev PI., Papoian GA. Molecular noise of capping protein binding induces macroscopic instability in filopodial dynamics. Proc. Natl. Acad. Sci. U.S.A. 2009; 106(28). [PMID: 19556544]
  29. Sheetz MP., Wayne DB., Pearlman AL. Extension of filopodia by motor-dependent actin assembly. Cell Motil. Cytoskeleton 1992; 22(3). [PMID: 1423662]
  30. Schirenbeck A., Bretschneider T., Arasada R., Schleicher M., Faix J. The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia. Nat. Cell Biol. 2005; 7(6). [PMID: 15908944]
  31. Tornieri K., Welshhans K., Geddis MS., Rehder V. Control of neurite outgrowth and growth cone motility by phosphatidylinositol-3-kinase. Cell Motil. Cytoskeleton 2006; 63(4). [PMID: 16463277]
  32. Medalia O., Beck M., Ecke M., Weber I., Neujahr R., Baumeister W., Gerisch G. Organization of actin networks in intact filopodia. Curr. Biol. 2007; 17(1). [PMID: 17208190]
  33. Costantino S., Kent CB., Godin AG., Kennedy TE., Wiseman PW., Fournier AE. Semi-automated quantification of filopodial dynamics. J. Neurosci. Methods 2008; 171(1). [PMID: 18394712]
  34. Miller J., Fraser SE., McClay D. Dynamics of thin filopodia during sea urchin gastrulation. Development 1995; 121(8). [PMID: 7671814]
  35. Oldenbourg R., Katoh K., Danuser G. Mechanism of lateral movement of filopodia and radial actin bundles across neuronal growth cones. Biophys. J. 2000; 78(3). [PMID: 10692307]
  36. Steketee MB., Tosney KW. Three functionally distinct adhesions in filopodia: shaft adhesions control lamellar extension. J. Neurosci. 2002; 22(18). [PMID: 12223561]
  37. Steketee M., Balazovich K., Tosney KW. Filopodial initiation and a novel filament-organizing center, the focal ring. Mol. Biol. Cell 2001; 12(8). [PMID: 11514623]
  38. Mitchison T., Kirschner M. Cytoskeletal dynamics and nerve growth. Neuron 1988; 1(9). [PMID: 3078414]
  39. Lamoureux P., Buxbaum RE., Heidemann SR. Direct evidence that growth cones pull. Nature 1989; 340(6229). [PMID: 2739738]
  40. Bastmeyer M., Stuermer CA. Behavior of fish retinal growth cones encountering chick caudal tectal membranes: a time-lapse study on growth cone collapse. J. Neurobiol. 1993; 24(1). [PMID: 8419523]
  41. Raich WB., Agbunag C., Hardin J. Rapid epithelial-sheet sealing in the Caenorhabditis elegans embryo requires cadherin-dependent filopodial priming. Curr. Biol. 1999; 9(20). [PMID: 10531027]
  42. Vasioukhin V., Bauer C., Yin M., Fuchs E. Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 2000; 100(2). [PMID: 10660044]
  43. Renaudin A., Lehmann M., Girault J., McKerracher L. Organization of point contacts in neuronal growth cones. J. Neurosci. Res. 1999; 55(4). [PMID: 10723056]
  44. Gomez TM., Roche FK., Letourneau PC. Chick sensory neuronal growth cones distinguish fibronectin from laminin by making substratum contacts that resemble focal contacts. J. Neurobiol. 1996; 29(1). [PMID: 8748369]
  45. Woo S., Gomez TM. Rac1 and RhoA promote neurite outgrowth through formation and stabilization of growth cone point contacts. J. Neurosci. 2006; 26(5). [PMID: 16452665]
  46. Bershadsky AD., Ballestrem C., Carramusa L., Zilberman Y., Gilquin B., Khochbin S., Alexandrova AY., Verkhovsky AB., Shemesh T., Kozlov MM. Assembly and mechanosensory function of focal adhesions: experiments and models. Eur. J. Cell Biol. 2006; 85(3-4). [PMID: 16360240]
  47. Yuan XB., Jin M., Xu X., Song YQ., Wu CP., Poo MM., Duan S. Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nat. Cell Biol. 2003; 5(1). [PMID: 12510192]
  48. Luikart BW., Zhang W., Wayman GA., Kwon CH., Westbrook GL., Parada LF. Neurotrophin-dependent dendritic filopodial motility: a convergence on PI3K signaling. J. Neurosci. 2008; 28(27). [PMID: 18596174]
  49. Song H., Poo M. The cell biology of neuronal navigation. Nat. Cell Biol. 2001; 3(3). [PMID: 11231595]
  50. Gallo G., Letourneau PC. Regulation of growth cone actin filaments by guidance cues. J. Neurobiol. 2004; 58(1). [PMID: 14598373]
  51. Nishizaka T., Shi Q., Sheetz MP. Position-dependent linkages of fibronectin- integrin-cytoskeleton. Proc. Natl. Acad. Sci. U.S.A. 2000; 97(2). [PMID: 10639141]
  52. Lehmann MJ., Sherer NM., Marks CB., Pypaert M., Mothes W. Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells. J. Cell Biol. 2005; 170(2). [PMID: 16027225]
  53. Bose KS., Sarma RH. Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. Biochem. Biophys. Res. Commun. 1975; 66(4). [PMID: 2]
  54. Onfelt B., Nedvetzki S., Benninger RK., Purbhoo MA., Sowinski S., Hume AN., Seabra MC., Neil MA., French PM., Davis DM. Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J. Immunol. 2006; 177(12). [PMID: 17142745]
  55. Nagafusa T., Hoshino H., Sakurai T., Terakawa S., Nagano A. Mechanical fragmentation and transportation of calcium phosphate substrate by filopodia and lamellipodia in a mature osteoclast. Cell Biol. Int. 2007; 31(10). [PMID: 17498977]
  56. Fan J., Mansfield SG., Redmond T., Gordon-Weeks PR., Raper JA. The organization of F-actin and microtubules in growth cones exposed to a brain-derived collapsing factor. J. Cell Biol. 1993; 121(4). [PMID: 8491778]
  57. Jurney WM., Gallo G., Letourneau PC., McLoon SC. Rac1-mediated endocytosis during ephrin-A2- and semaphorin 3A-induced growth cone collapse. J. Neurosci. 2002; 22(14). [PMID: 12122063]
  58. Kress H., Stelzer EH., Holzer D., Buss F., Griffiths G., Rohrbach A. Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity. Proc. Natl. Acad. Sci. U.S.A. 2007; 104(28). [PMID: 17620618]
  59. Beck ML., Freihaut B., Henry R., Pierce S., Bayer WL. A serum haemagglutinating property dependent upon polycarboxyl groups. Br. J. Haematol. 1975; 29(1). [PMID: 32]
  60. Mier PD., van den Hurk JJ. Lysosomal hydrolases of the epidermis. 2. Ester hydrolases. Br. J. Dermatol. 1975; 93(4). [PMID: 31]
  61. Corrocher R., Tedesco F., Rabusin P., De Sandre G. Effect of human erythrocyte stromata on complement activation. Br. J. Haematol. 1975; 29(2). [PMID: 33]
  62. Warth J., Desforges JF. Determinants of intracellular pH in the erythrocyte. Br. J. Haematol. 1975; 29(3). [PMID: 34]
  63. Zhou FQ., Cohan CS. Growth cone collapse through coincident loss of actin bundles and leading edge actin without actin depolymerization. J. Cell Biol. 2001; 153(5). [PMID: 11381091]
  64. Lin CH., Espreafico EM., Mooseker MS., Forscher P. Myosin drives retrograde F-actin flow in neuronal growth cones. Neuron 1996; 16(4). [PMID: 8607995]
  65. RhoA-kinase coordinates F-actin organization and myosin II activity during semaphorin-3A-induced axon retraction. J. Cell. Sci. 2006; 119(Pt 16). [PMID: 16899819]
  66. Walter J., Allsopp TE., Bonhoeffer F. A common denominator of growth cone guidance and collapse? Trends Neurosci. 1990; 13(11). [PMID: 1701577]
  67. Liu BP., Strittmatter SM. Semaphorin-mediated axonal guidance via Rho-related G proteins. Curr. Opin. Cell Biol. 2001; 13(5). [PMID: 11544032]
  68. Aizawa H., Wakatsuki S., Ishii A., Moriyama K., Sasaki Y., Ohashi K., Sekine-Aizawa Y., Sehara-Fujisawa A., Mizuno K., Goshima Y., Yahara I. Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat. Neurosci. 2001; 4(4). [PMID: 11276226]
  69. Sasaki Y., Cheng C., Uchida Y., Nakajima O., Ohshima T., Yagi T., Taniguchi M., Nakayama T., Kishida R., Kudo Y., Ohno S., Nakamura F., Goshima Y. Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron 2002; 35(5). [PMID: 12372285]
  70. Eickholt BJ., Walsh FS., Doherty P. An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling. J. Cell Biol. 2002; 157(2). [PMID: 11956225]
  71. Luo Y., Raible D., Raper JA. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993; 75(2). [PMID: 8402908]
  72. Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K. Dev Neurobiol 2008; 68(7). [PMID: 18327764]
  73. Bretscher A., Edwards K., Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 2002; 3(8). [PMID: 12154370]
Updated on: Mon, 20 Oct 2014 09:21:54 GMT