Nucleation, stabilization, and disassembly of branched actin networks

Gautreau, Alexis; Fregoso, Fred E.; Simanov, Gleb; Domínguez, Roberto

doi:10.1016/j.tcb.2021.10.006

Cited by 92 publications

(101 citation statements)

References 98 publications

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“…Actin-related protein (Arp): Arp2 and Arp3 are part of the Arp2/3 complex, which does not nucleate actin de novo, but promotes polymerization in the presence of both preexisting F-actin and a nucleation promotion factor (NPF) such as WASP/WAVE. Activated NPFs bind to both G-actin and the Arp2/3 complex to initiate the binding of Arp2/3 to the preexisting F-actin and nucleation [60,61].…”

Section: How Abps Interact With Actinmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.

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Section: How Abps Interact With Actinmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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“…Branched actin filament networks, such as the ones found in the lamellipodia of migrating cells, or in endocytic patches, are a hallmark example of dynamic actin networks in cells. Branches result from the activation of the Arp2/3 complex by the VCA domains of nucleation-promoting factors (NPFs), such as WASP or WAVE (See (Gautreau et al, 2022) for a review). The VCA domain binds to the Arp2/3 complex via its CA domain, and recruits an actin monomer (G-actin) via its V-domain (also known as WH2 domain).…”

Section: Introductionmentioning

confidence: 99%

Nucleation and stability of branched versus linear Arp2/3-generated actin filaments

Cao

Ghasemi

Way

et al. 2022

Preprint

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Activation of the Arp2/3 complex by VCA-domain-bearing NPFs results in the formation of "daughter" actin filaments branching off the sides of pre-existing "mother filaments." Alternatively, when stimulated by SPIN90, Arp2/3 directly nucleates "linear" actin filaments. Uncovering the similarities and differences of these two activation mechanisms is fundamental to understanding the regulation and function of Arp2/3. Analysis of individual filaments reveals that the catalytic VCA domain of WASP, N-WASP and WASH, accelerate the Arp2/3-mediated nucleation of linear filaments by SPIN90, in addition to their known branch-promoting activity. Unexpectedly, these VCA domains also destabilize existing branches, as well as SPIN90-Arp2/3 at filament pointed ends. Furthermore, cortactin and GMF, which respectively stabilize and destabilize Arp2/3 at branch junctions, have a similar impact on SPIN90-activated Arp2/3. However, unlike branch junctions, SPIN90-Arp2/3 at the pointed end of linear filaments is not destabilized by piconewton forces, and does not become less stable with time. It thus appears that linear and branched Arp2/3-generated filaments respond similarly to regulatory proteins, albeit with quantitative differences, and that they differ greatly in their responses to aging and to mechanical stress. These results indicate that SPIN90- and VCA-activated Arp2/3 complexes adopt similar yet non-identical conformations, and that their turnover in cells may be regulated differently.

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“…Many diverse cell processes such as cell division, motility, and shape changes require that actin filaments be organized into assemblies of optimized architecture, dynamics, and mechanical attributes to carry out their specific functions properly (Boiero Sanders et al, 2020; Campellone and Welch, 2010; Cheffings et al, 2016; Gautreau et al, 2021; Schwayer et al, 2016). We find that during cell wound repair the proper assembly and function of the actomyosin ring requires both branched and linear actin networks (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…While all WAS family members, along with Arp2/3, promote the generation of branched actin networks, specific family members can be called upon to perform specialized functions within the cell (Burianek and Soderling, 2013; Massaad et al, 2013). These non-redundant functions are often associated with the variable N-terminal domains of WAS family proteins that mediate different protein interactions leading to variations in the architecture of their actin assemblies (Gautreau et al, 2021; Molinie and Gautreau, 2018). Interestingly, WASp, Wash, and SCAR are all required for cell wound repair, where they exhibit different spatiotemporal recruitments and phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Cell wound repair requires the coordinated action of linear and branched actin nucleation factors

Hui

Nakamura

Dubrulle

et al. 2022

Preprint

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Cells are subjected to a barrage of daily insults that often lead to its cortex being ripped open and requiring immediate repair. An important component of the cell′s repair response is the formation of an actomyosin ring at the wound periphery to mediate its closure. Inhibition of linear actin nucleation factors and myosin result in a disrupted contractile apparatus and delayed wound closure. Here we show that branched actin nucleators function as a scaffold to assemble and maintain this contractile actomyosin cable. Removing branched actin leads to the formation of smaller circular actin-myosin structures at the cell cortex and slow wound closure. Removing linear and branched actin results in failed wound closure. Surprisingly, removal of branched actin and myosin results in the formation of parallel linear actin filaments that undergo a chiral swirling movement to close the wound. These results provide insight into actin organization in contractile actomyosin rings and uncover a new mechanism of wound closure.

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Nucleation, stabilization, and disassembly of branched actin networks

Cited by 92 publications

References 98 publications

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Nucleation and stability of branched versus linear Arp2/3-generated actin filaments

Cell wound repair requires the coordinated action of linear and branched actin nucleation factors

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