Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

Jiu, Yaming; Kumari, Reena; Fenix, Aidan M.; Schaible, Niccole; Liu, Xiaonan; Varjosalo, Markku; Krishnan, Ramaswamy; Burnette, Dylan T.; Lappalainen, Pekka

doi:10.1016/j.cub.2018.11.045

Cited by 46 publications

(54 citation statements)

References 45 publications

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“…Given that the phosphorylation status of NMHC2A Tyr 158 regulates the dynamics of the actomyosin bundles, it is possible that the phosphorylation on Tyr 158 modulates the assembly and function of NM2 stacks, which are important for cytoskeleton remodeling and impact cell morphogenesis and migration [71]. The cellular mechanisms that drive morphogenesis depend on adhesion forces and on the activity of the actomyosin filaments [72], which are important in tissue wound healing and developmental closure events [73].…”

Section: Discussionmentioning

confidence: 99%

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

Brito

Mesquita

Osório

et al. 2020

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Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that along with actin assembles into actomyosin filaments inside cells. NM2A is fundamental in cellular processes requiring force generation such as cell adhesion, motility and cell division, and plays important functions in different stages of development and during the progression of viral and bacterial infections. We previously identified at the motor domain of the NM2A, a novel Src-dependent tyrosine phosphorylation on residue 158 (pTyr158), which is promoted by Listeria monocytogenes infection. Despite the central role of NM2A in several cell biology processes, the pTyr at this specific residue had never been reported. Here we showed that LLO, a toxin secreted by Listeria, is sufficient to trigger NM2A pTyr158 by activating Src, which coordinates actomyosin remodeling. We further addressed the role of NM2A pTyr158 on the organization and dynamics of the actomyosin cytoskeleton and found that by controlling the activation of the NM2A, the status of the pTyr158 alters cytoskeletal organization, dynamics of focal adhesions and cell motility, without affecting NM2A enzymatic activity in vitro. Ultimately, by using Caenorhabditis elegans as a model to assess the role of this pTyr158 in vivo, we found that the status of the pTyr158 has implications in gonad function and is required for organism survival under stress conditions. We conclude that the fine control of the NM2A pTyr158 is required for cell cytoskeletal remodeling and dynamics, and we propose Src-dependent NM2A pTyr158 as a novel layer of regulation of the actomyosin cytoskeleton.

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Section: Discussionmentioning

confidence: 99%

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

Brito

Mesquita

Osório

et al. 2020

Preprint

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“…Transverse arcs, on the other hand, are thin, contractile actomyosin bundles, arising through NMII-promoted condensing of the lamellipodial actin network at the cell edge (Burnette et al, 2011;Hotulainen and Lappalainen, 2006;Tojkander et al, 2011). Following their appearance, transverse arcs undergo retrograde flow towards the cell center, fuse with each other into thicker bundles, and become more contractile due to concatenation and persistent expansion of NMII filaments into stacks (Beach et al, 2017;Fenix et al, 2016;Hu et al, 2017;Jiu et al, 2019;Tojkander et al, 2015). Although transverse arcs are not directly linked to focal adhesions, they associate with focal adhesion -connected dorsal stress fibers (Burnette et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Generation of stress fibers through myosin-driven re-organization of the actin cortex

Lehtimäki

Rajakylä

Tojkander

et al. 2020

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SummaryContractile actomyosin bundles, stress fibers, govern key cellular processes including migration, adhesion, and mechanosensing. Stress fibers are thus critical for developmental morphogenesis. The most prominent actomyosin bundles, ventral stress fibers, are generated through coalescence of pre-existing stress fiber precursors. However, whether stress fibers can assemble through other mechanisms has remained elusive. We report that stress fibers can also form without requirement of pre-existing actomyosin bundles. These structures, which we named cortical stress fibers, are embedded in the cell cortex and assemble preferentially underneath the nucleus. In this process, non-muscle myosin II pulses orchestrate the reorganization of cortical actin meshwork into regular bundles, which promote reinforcement of nascent focal adhesions, and subsequent stabilization of the cortical stress fibers. These results identify a new mechanism by which stress fibers can be generated de novo from the actin cortex, and establish role for stochastic myosin pulses in the assembly of functional actomyosin bundles.

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“…the Rho-pathway, nonmuscle myosin II 7 (NM2) is assembled into minifilaments with approximately 30 single myosins [3,4], 8 forming a supra-molecular complex with a size around 300 nm that traditionally is 9 investigated with electron microscopy [5,6]. Only recently has live cell super-resolution 10 microscopy made it possible to image the dynamics of NM2-minifilaments in cells [7][8][9][10][11]. 11 This revealed many unexpected processes, including splitting, expansion, concatenation, 12 long-range attraction and stacking.…”

Section: Introductionmentioning

confidence: 99%

“…Only recently has live cell super-resolution 10 microscopy made it possible to image the dynamics of NM2-minifilaments in cells [7][8][9][10][11]. 11 This revealed many unexpected processes, including splitting, expansion, concatenation, 12 long-range attraction and stacking. Moreover it was observed that single myosin 13 monomers have a relatively high exchange rate [10] and that the three human 14 NM2-isoforms A, B and C dynamically mix [12].…”

Section: Introductionmentioning

confidence: 99%

Electrostatic and bending energies predict staggering and splaying in nonmuscle myosin II minifilaments

Kaufmann

Schwarz

2020

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Recent experiments with super-resolution live cell microscopy revealed that nonmuscle myosin II minifilaments are much more dynamic than formerly appreciated, often showing plastic processes such as splitting, concatenation and stacking. Here we combine sequence information, electrostatics and elasticity theory to demonstrate that the parallel staggers at 14.3, 43.2 and 72 nm have a strong tendency to splay their heads away from the minifilament, thus potentially initiating the diverse processes seen in live cells. In contrast, the straight antiparallel stagger with an overlap of 43 nm is very stable and likely initiates minifilament nucleation. Using stochastic dynamics in a newly defined energy landscape, we predict that the optimal parallel staggers between the myosin rods are obtained by a trial-and-error process in which two rods attach and re-attach at different staggers by rolling and zipping motion. The experimentally observed staggers emerge as the configurations with the largest contact times. We find that contact times increase from isoforms C to B to A, that A-B-heterodimers are surprisingly stable and that myosin 18A should incorporate into mixed filaments with a small stagger. Our findings suggest that nonmuscle myosin II minifilaments in the cell are first formed by isoform A and then convert to mixed A-B-filaments, as observed experimentally. Author summaryNonmuscle myosin II (NM2) is a non-processive molecular motor that assembles into minifilaments with a typical size of 300 nm to generate force and motion in the actin cytoskeleton. This process is essential for many cellular processes such as adhesion, migration, division and mechanosensing. Due to their small size below the resolution limit, minifilaments are a challenge for imaging with traditional light microscopy. With the advent of super-resolution microscopy, however, it has become apparent that the formation of NM2-minifilaments is much more dynamic than formerly appreciated. Modeling the electrostatic interaction between the rigid rods of the myosin monomers has confirmed the main staggers observed in experiments, but cannot explain these high dynamics. Here we complement electrostatics by elasticity theory and stochastic dynamics to show that the parallel staggers are likely to splay away from the main axis of the minifilament and that monomers attach and deattach with rolling and zipping motions. Based on the sequences of the different NM2-isoforms, we predict that isoform A forms the most stable homofilaments and that A-B-heterofilaments are also very stable.

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Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

Cited by 46 publications

References 45 publications

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

Generation of stress fibers through myosin-driven re-organization of the actin cortex

Electrostatic and bending energies predict staggering and splaying in nonmuscle myosin II minifilaments

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