scholarly journals MICAL2 fine-tunes Arp2/3 for actin branching

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Michael F. Olson ◽  
Laura M. Machesky
Keyword(s):  
Actin Filaments ◽  
Methionine Oxidation ◽  
Actin Networks ◽  
Cell Biol ◽  
Subunit Isoforms

The ARP2/3 complex promotes branched actin networks, but the importance of specific subunit isoforms is unclear. In this issue, Galloni, Carra, et al. (2021. J. Cell Biol. https://doi.org/10.1083/jcb.202102043) show that MICAL2 mediates methionine oxidation of ARP3B, thus destabilizing ARP2/3 complexes and leading to disassembly of branched actin filaments.

scholarly journals Elasticity of dense actin networks produces nanonewton protrusive forces

2021 ◽  
Author(s):  
Marion Jasnin ◽  
Jordan Hervy ◽  
Stéphanie Balor ◽  
Anais Bouissou ◽  
Amsha Proag ◽  
...  
Keyword(s):  
Actin Filaments ◽  
Actin Polymerization ◽  
Electron Tomography ◽  
Force Production ◽  
Basal Membrane ◽  
Theoretical Modelling ◽  
Elastic Behavior ◽  
Integrative Approach ◽  
Cellular Functions ◽  
Actin Networks

AbstractActin filaments assemble into force-generating systems involved in diverse cellular functions, including cell motility, adhesion, contractility and division. It remains unclear how networks of actin filaments, which individually generate piconewton forces, can produce forces reaching tens of nanonewtons. Here we use in situ cryo-electron tomography to unveil how the nanoscale architecture of macrophage podosomes enables basal membrane protrusion. We show that the sum of the actin polymerization forces at the membrane is not sufficient to explain podosome protrusive forces. Quantitative analysis of podosome organization demonstrates that the core is composed of a dense network of bent actin filaments storing elastic energy. Theoretical modelling of the network as a spring-loaded elastic material reveals that it exerts forces of up to tens of nanonewtons, similar to those evaluated experimentally. Thus, taking into account not only the interface with the membrane but also the bulk of the network, is crucial to understand force generation by actin machineries. Our integrative approach sheds light on the elastic behavior of dense actin networks and opens new avenues to understand force production inside cells.

scholarly journals Modulation of formin processivity by profilin and mechanical tension

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Luyan Cao ◽  
Mikael Kerleau ◽  
Emiko L. Suzuki ◽  
Hugo Wioland ◽  
Sandy Jouet ◽  
...  
Keyword(s):  
Actin Filaments ◽  
Dissociation Rate ◽  
Actin Networks ◽  
Filament Dynamics ◽  
Open Questions ◽  
Microfluidic Flow ◽  
Tensile Forces ◽  
Mechanical Factors ◽  
Transient Contact ◽  
Actin Concentration

Formins are major regulators of actin networks. They enhance actin filament dynamics by remaining processively bound to filament barbed ends. How biochemical and mechanical factors affect formin processivity are open questions. Monitoring individual actin filaments in a microfluidic flow, we report that formins mDia1 and mDia2 dissociate faster under higher ionic strength and when actin concentration is increased. Profilin, known to increase the elongation rate of formin-associated filaments, surprisingly decreases the formin dissociation rate, by bringing formin FH1 domains in transient contact with the barbed end. In contrast, piconewton tensile forces applied to actin filaments accelerate formin dissociation by orders of magnitude, largely overcoming profilin-mediated stabilization. We developed a model of formin conformations showing that our data indicates the existence of two different dissociation pathways, with force favoring one over the other. How cells limit formin dissociation under tension is now a key question for future studies.

scholarly journals A consistent picture of the actin filament related to the orientation of the actin molecule.

1983 ◽  
Vol 97 (1) ◽  
pp. 264-269 ◽  
Author(s):  
W E Fowler ◽  
U Aebi
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Cell Biol ◽  
Freeze Dried ◽  
Consistent Picture

We show that freeze-dried actin filaments which have been rotary shadowed with a light coat of platinum appear very similar in morphology and width to negatively-stained filaments. The addition of a thicker coat of platinum to such preparations gives the actin filaments a different morphology and width, which are similar to those of the rotary-shadowed, quick-frozen filaments described by Heuser and Kirschner (J. Cell Biol. 1980, 86:212-234). The consistent view of the actin filament presented here, particularly its 7-8-nm width, can be interpreted in terms of the overall orientation of the actin subunit in the actin filament.

scholarly journals Effect of actin-binding protein on the sedimentation properties of actin.

1982 ◽  
Vol 94 (1) ◽  
pp. 51-55 ◽  
Author(s):  
S Rosenberg ◽  
A Stracher
Keyword(s):  
Actin Filaments ◽  
Human Platelet ◽  
Binding Protein ◽  
Actin Binding ◽  
Cross Linking ◽  
Actin Binding Protein ◽  
Cell Biol

Actin and actin-binding protein (ABP) have recently been purified from human platelet cytoskeletons (S. Rosenberg, A. Stracher, and R.C. Lucas, 1981, J. Cell Biol. 91:201-211). Here, the effect of ABP on the sedimentation of actin was studied. When ABP was added to preformed F-actin filaments, it bound until a maximum ratio of 1:9 (ABP:actin, mol:mol) was reached. however, when actin was polymerized in the presence of ABP, two and a half times more ABP was able to bind to the actin- that is, every 3.4 actin monomers were now bound by an ABP dimer. ABP was not able to induce the sedimentation of actin under nonpolymerizing conditions but was able to reduce the time and concentration of actin required for sedimentation under slow polymerizing conditions. ABP, therefore, exerts its effect of G-actin by either nucleating polymerization or by cross-linking newly formed oligomers into a more sedimentable form.

scholarly journals Crosslinking actin networks produces compressive force

2019 ◽  
Author(s):  
Rui Ma ◽  
Julien Berro
Keyword(s):  
Actin Filaments ◽  
Brownian Dynamics ◽  
Actin Polymerization ◽  
Turgor Pressure ◽  
Compressive Force ◽  
Yeast Cells ◽  
Actin Networks ◽  
Dynamics Simulations ◽  
Brownian Dynamics Simulations ◽  
Over Time

AbstractActin has been shown to be essential for clathrin-mediated endocytosis in yeast. However, actin polymerization alone is likely insufficient to produce enough force to deform the membrane against the huge turgor pressure of yeast cells. In this paper, we used Brownian dynamics simulations to demonstrate that crosslinking of a meshwork of non-polymerizing actin filaments is able to produce compressive forces. We show that the force can be up to thousands of piconewtons if the crosslinker has a high stiffness. The force decays over time as a result of crosslinker turnover, and is a result of converting chemical binding energy into elastic energy.

scholarly journals Synergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shashank Shekhar ◽  
Johnson Chung ◽  
Jane Kondev ◽  
Jeff Gelles ◽  
Bruce L. Goode
Keyword(s):  
Actin Filament ◽  
Single Molecule ◽  
Actin Filaments ◽  
Binding Protein ◽  
Actin Dynamics ◽  
Actin Network ◽  
Cellular Mechanisms ◽  
Actin Networks ◽  
Binding Event

AbstractCellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize slowly over minutes. The cellular mechanisms enabling actin to depolymerize this fast have so far remained obscure. Using microfluidics-assisted TIRF, we show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends at a rate 330-fold faster than spontaneous depolymerization. Single molecule imaging further reveals that hexameric CAP molecules interact with the pointed ends of Cofilin-decorated filaments for several seconds at a time, removing approximately 100 actin subunits per binding event. These findings establish a paradigm, in which a filament end-binding protein and a side-binding protein work in concert to control actin dynamics, and help explain how rapid actin network depolymerization is achieved in cells.

scholarly journals A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Johanna Funk ◽  
Felipe Merino ◽  
Matthias Schaks ◽  
Klemens Rottner ◽  
Stefan Raunser ◽  
...  
Keyword(s):  
Structural Biology ◽  
Actin Filaments ◽  
Actin Network ◽  
Essential Factor ◽  
Actin Networks ◽  
Capping Protein ◽  
Cellular Processes ◽  
In Vitro Reconstitution ◽  
Interference Mechanism

AbstractHeterodimeric capping protein (CP/CapZ) is an essential factor for the assembly of branched actin networks, which push against cellular membranes to drive a large variety of cellular processes. Aside from terminating filament growth, CP potentiates the nucleation of actin filaments by the Arp2/3 complex in branched actin networks through an unclear mechanism. Here, we combine structural biology with in vitro reconstitution to demonstrate that CP not only terminates filament elongation, but indirectly stimulates the activity of Arp2/3 activating nucleation promoting factors (NPFs) by preventing their association to filament barbed ends. Key to this function is one of CP’s C-terminal “tentacle” extensions, which sterically masks the main interaction site of the terminal actin protomer. Deletion of the β tentacle only modestly impairs capping. However, in the context of a growing branched actin network, its removal potently inhibits nucleation promoting factors by tethering them to capped filament ends. End tethering of NPFs prevents their loading with actin monomers required for activation of the Arp2/3 complex and thus strongly inhibits branched network assembly both in cells and reconstituted motility assays. Our results mechanistically explain how CP couples two opposed processes—capping and nucleation—in branched actin network assembly.

Regulation of Actin Assembly Associated With Protrusion and Adhesion in Cell Migration

2008 ◽  
Vol 88 (2) ◽  
pp. 489-513 ◽  
Author(s):  
Christophe Le Clainche ◽  
Marie-France Carlier
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Actin Assembly ◽  
Concerted Action ◽  
Actin Networks ◽  
Capping Proteins ◽  
Cell Matrix ◽  
A Cell ◽  
Actomyosin Contraction

To migrate, a cell first extends protrusions such as lamellipodia and filopodia, forms adhesions, and finally retracts its tail. The actin cytoskeleton plays a major role in this process. The first part of this review (sect. ii) describes the formation of the lamellipodial and filopodial actin networks. In lamellipodia, the WASP-Arp2/3 pathways generate a branched filament array. This polarized dendritic actin array is maintained in rapid treadmilling by the concerted action of ADF, profilin, and capping proteins. In filopodia, formins catalyze the processive assembly of nonbranched actin filaments. Cell matrix adhesions mechanically couple actin filaments to the substrate to convert the treadmilling into protrusion and the actomyosin contraction into traction of the cell body and retraction of the tail. The second part of this review (sect. iii) focuses on the function and the regulation of major proteins (vinculin, talin, tensin, and α-actinin) that control the nucleation, the binding, and the barbed-end growth of actin filaments in adhesions.

scholarly journals Interactions with Actin Monomers, Actin Filaments, and Arp2/3 Complex Define the Roles of WASP Family Proteins and Cortactin in Coordinately Regulating Branched Actin Networks

2014 ◽  
Vol 289 (42) ◽  
pp. 28856-28869 ◽  
Author(s):  
Luke A. Helgeson ◽  
Julianna G. Prendergast ◽  
Andrew R. Wagner ◽  
Max Rodnick-Smith ◽  
Brad J. Nolen
Keyword(s):  
Actin Filaments ◽  
Actin Networks ◽  
Wasp Family Proteins
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