A mechanism of leading-edge protrusion in the absence of Arp2/3 complex

Suraneni, Praveen; Fogelson, Ben; Rubinstein, Boris; Noguera, Philippe; Volkmann, Niels; Hanein, Dorit; Mogilner, Alex; Li, Rong

doi:10.1091/mbc.e14-07-1250

Cited by 45 publications

(84 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that the Rac/WAVE/Arp2/3 complex pathway is essential for generation and maintenance of lamellipodia681011405153545556. Much less is known about how actin filament elongators such as formins and Ena/VASP family proteins contribute to protrusion and thus lamellipodia-dependent migration121457.…”

Section: Discussionmentioning

confidence: 99%

FMNL formins boost lamellipodial force generation

et al. 2017

View full text Add to dashboard Cite

Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.

show abstract

Section: Discussionmentioning

confidence: 99%

FMNL formins boost lamellipodial force generation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…For example, depletion or inactivation of Arp2/3 complex in fibroblasts results in the disappearance of lamellipodia and an increase in filopodia formation, likely by incorporation of the released pool of G-actin by formin or Ena/VASP (Figure 3 D) 7,12,47,48 . A similar Arp2/3 complex inactivation phenotype has also been reported in other cell types such as Drosophila S2, human osteosarcoma U2OS, rat adenocarcinoma MTLn3, Coelomocytes and Aplysia neuronal growth cones (Figure 3 E) 49–54 .…”

Section: Introductionmentioning

confidence: 99%

“…For example, disruption of Arp2/3 complex-mediated lamellipodia leads to an increase of filopodia at the leading edge of migrating cells 7,12,48 . One interpretation may be that Arp2/3 complex-generated branched actin filaments are not critical for filopodia assembly 9 .…”

Section: Introductionmentioning

confidence: 99%

Internetwork competition for monomers governs actin cytoskeleton organization

Suarez

Kovar

2016

Nat Rev Mol Cell Biol

158

133

View full text Add to dashboard Cite

Cells precisely control the formation of dynamic actin cytoskeletal networks to coordinate fundamental processes including motility, division, endocytosis and polarization. To support these functions, actin filament networks must be assembled, maintained and disassembled at the correct time and place, and with proper filament organization and dynamics. Regulation of the extent of filament network assembly and their organization have been largely attributed to the coordinated activation of actin assembly factors through signalling cascades. Here we discuss an intriguing model in which actin monomer availability is limiting, and competition between homeostatic actin cytoskeletal networks for actin monomers is an additional crucial regulatory mechanism that influences density and size of different actin networks, thereby contributing to the organization of the cellular actin cytoskeleton.

show abstract

“…Surprisingly, these Arp2/3-deficient cells are still migratory, though with reduced speed, through the generation of formin-containing filopodial structures of bundled actin [45,46]. These actin structures coordinate with myosin II-mediated contractility in the cortex to drive leading edge extension [44]. Although these studies found similar alterations in F-actin structures at the leading edge, they disagreed on the effect of Arp2/3 complex loss on migration toward chemical cues: our studies showed reduced directional persistence and a cell-autonomous defect in chemotaxis toward growth factors, while Wu et al found that Arp2/3 knock-down cells only exhibit a chemotactic deficiency if there is interference by secreted inflammatory cytokines [44,47].…”

Section: Introductionmentioning

confidence: 99%

“…These actin structures coordinate with myosin II-mediated contractility in the cortex to drive leading edge extension [44]. Although these studies found similar alterations in F-actin structures at the leading edge, they disagreed on the effect of Arp2/3 complex loss on migration toward chemical cues: our studies showed reduced directional persistence and a cell-autonomous defect in chemotaxis toward growth factors, while Wu et al found that Arp2/3 knock-down cells only exhibit a chemotactic deficiency if there is interference by secreted inflammatory cytokines [44,47]. The same group did find that haptotaxis toward surface-bound ECM molecules is impaired in the knock-down cells and later repeated their findings with an Arp2/3 subunit knock-out [43,46].…”

Section: Introductionmentioning

confidence: 99%

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

Swaney

2016

Current Opinion in Cell Biology

Self Cite

View full text Add to dashboard Cite

As the first de novo actin nucleator discovered, the Arp2/3 complex has been a central player in models of protrusive force production via the dynamic actin network. Here, we review recent studies on the functional role of the Arp2/3 complex in the migration of diverse cell types in different migratory environments. These findings have revealed an unexpected level of plasticity, both in how cells rely on the Arp2/3 complex for migration and other physiological functions and in the intricate modulation of the Arp2/3 complex by other actin regulators and upstream signaling cascades.

show abstract

A mechanism of leading-edge protrusion in the absence of Arp2/3 complex

Cited by 45 publications

References 51 publications

FMNL formins boost lamellipodial force generation

FMNL formins boost lamellipodial force generation

Internetwork competition for monomers governs actin cytoskeleton organization

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

Contact Info

Product

Resources

About