Myosin-X: a molecular motor at the cell's fingertips

Sousa, Aurea D.; Cheney, Richard E.

doi:10.1016/j.tcb.2005.08.006

Cited by 113 publications

(121 citation statements)

References 73 publications

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“…In contrast to actin, myosin II in the retraction fibers exhibited motion both toward the cell body and away from it ( Figure 3, B and C). Similar patterns of motion were reported previously in filopodia for myosin X (Sousa and Cheney, 2005). Motion away from the cell body is consistent with myosin motor polarity and actin filament polarity in retraction fibers with barbed ends toward the tip of the fiber (Svitkina et al, 1997).…”

Section: Dynamics Of Actin and Myosin II In The Retraction Fiberssupporting

confidence: 88%

Comparative Maps of Motion and Assembly of Filamentous Actin and Myosin II in Migrating Cells

Schaub

Bohnet

Laurent

et al. 2007

MBoC

120

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To understand the mechanism of cell migration, one needs to know how the parts of the motile machinery of the cell are assembled and how they move with respect to each other. Actin and myosin II are thought to be the major structural and force-generating components of this machinery (Mitchison and Cramer, 1996; Parent, 2004). The movement of myosin II along actin filaments is thought to generate contractile force contributing to cell translocation, but the relative motion of the two proteins has not been investigated. We use fluorescence speckle and conventional fluorescence microscopy, image analysis, and computer tracking techniques to generate comparative velocity and assembly maps of actin and myosin II over the entire cell in a simple model system of persistently migrating fish epidermal keratocytes. The results demonstrate contrasting polarized assembly patterns of the two components, indicate force generation at the lamellipodium-cell body transition zone, and suggest a mechanism of anisotropic network contraction via sliding of myosin II assemblies along divergent actin filaments. INTRODUCTIONCrawling cell motion involves a cycle of several distinct processes: protrusion at the front of the cell, attachment to the substratum, and forward translocation of the cell body followed or accompanied by detachment and withdrawal of the rear of the cell. Crawling motion is thought to be dependent on the actin-myosin II cytoskeletal system (Mitchison and Cramer, 1996): protrusion is thought to be driven by the assembly of actin network, which is anchored to the substratum through integrin-containing adhesions; forward translocation of the cell body and contraction of the rear are thought to depend on the interaction of the actin network with the motor protein myosin II. Actin assembly during the protrusion at the leading edge of motile cells has recently received the most attention both in experimental (Pantaloni et al., 2001;Pollard and Borisy, 2003;Ridley et al., 2003) and theoretical studies (for review, see Mogilner, 2006). In contrast, the mechanisms involved in the forward translocation of the cell body remain largely unclear: the exact layout and the mode of action of the contractile actin-myosin II machinery are controversial. Qualitative models proposed in the literature include shortening of small contractile units similar to muscle sarcomeres, myosin II-dependent transport along uniformly polarized actin arrays, and a dynamic network contraction mechanism where contraction results from alignment of actin filaments by myosin II assemblies (Cramer, 1999;Verkhovsky et al., 1999a). More sophisticated biophysical models aim to understand the contractile cytoskeletal machinery in quantitative physical terms. In the past, considering the cytoskeleton as a gel made of cross-linked semiflexible polymers has helped understanding its passive visco-elastic properties. More recently, attempts were made to develop biophysical models taking into account intrinsic activity of the cytoskeleton: polarized assembly of acti...

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Section: Dynamics Of Actin and Myosin II In The Retraction Fiberssupporting

confidence: 88%

Comparative Maps of Motion and Assembly of Filamentous Actin and Myosin II in Migrating Cells

Schaub

Bohnet

Laurent

et al. 2007

MBoC

120

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“…Such an approach was previously used to break the myosin V lever arm after the second IQ domain (9). The linker of choice was (GSG) 2 as it has been previously used on anchoring domains on myosin VI (21). The introduction of flexibility into the system is motivated by myosin V, which contains a free swiveling joint between the two lever arms and before the coiled-coil domain, allowing for a spherical search for the most favorable binding site (1,22).…”

Section: Structural Properties Of the Tail Region Impart Fascin Bundlementioning

confidence: 99%

“…To begin to address these questions we have focused on a particular motor protein, myosin X, due to its ability to navigate to a precise location within the cell (2). Myosin X is found at the mitotic and meiotic spindle, where it sets the orientation of the spindle relative to the substrate and influences spindle length (3,4).…”

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confidence: 99%

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Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles

Nagy

Rock

2010

Journal of Biological Chemistry

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Without guidance cues, cytoskeletal motors would traffic components to the wrong destination with disastrous consequences for the cell. Recently, we identified a motor protein, myosin X, that identifies bundled actin filaments for transport. These bundles direct myosin X to a unique destination, the tips of cellular filopodia. Because the structural and kinetic features that drive bundle selection are unknown, we employed a domain-swapping approach with the nonselective myosin V to identify the selectivity module of myosin X. We found a surprising role of the myosin X tail region (post-IQ) in supporting long runs on bundles. Moreover, the myosin X head is adapted for initiating processive runs on bundles. We found that the tail is structured and biases the orientation of the two myosin X heads because a targeted insertion that introduces flexibility in the tail abolishes selectivity. Together, these results suggest how myosin motors may manage to read cellular addresses.The essential role of cytoskeletal motor proteins in organizing cellular compartments and cargoes is widely accepted (1). However, many of the molecular details of the overall transport and organization process are poorly understood. These essential features include how motors engage cargoes at their source, how motors are activated once they engage cargo, how they choose the correct set of cytoskeletal tracks, how they disengage from cargo at their destination, and how they return to sources of cargo. Clearly, errors at any of these stages would lead to faults in cellular organization and misplaced cargoes.To begin to address these questions we have focused on a particular motor protein, myosin X, due to its ability to navigate to a precise location within the cell (2). Myosin X is found at the mitotic and meiotic spindle, where it sets the orientation of the spindle relative to the substrate and influences spindle length (3, 4). However, myosin X is more commonly found in interphase cells at the tips of filopodia (5). These long, slender projections at the leading edge of migrating cells are involved in cell motility and environmental sensing. Myosin X transports components such as Ena/VASP and integrins that are found in the filopodial tip complex (2, 6). The early work by Berg et al. (5) demonstrated that myosin X reaches filopodial tips under its own power. Recently, we found that myosin X identifies filopodia by recognizing the fascin-bundled actin filaments found in the filopodial core (7). Myosin X takes long processive runs along these tightly bundled actin filaments while largely ignoring isolated actin filaments found throughout the cell. In contrast, myosin V does not distinguish between single actin filaments and bundled actin filaments when taking processive runs.Here, we seek to identify the "selectivity module" that allows myosin X to recognize bundled actin filaments. Our first approach is to swap similar domains between the selective myosin X and the nonselective myosin V. In this approach, we are aided by the fact that both m...

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“…organelle tip, effectively removing them from the picture, while they would still show in fluorescence. Localization at the tips is sometimes observed in fluorescence experiments (3,17). Whirlin, a scaffolding protein, would be one possible candidate for a motor immobilizer.…”

Section: Resultsmentioning

confidence: 96%

Theory of active transport in filopodia and stereocilia

Zhuravlev

Lan

Minakova

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The biological processes in elongated organelles of living cells are often regulated by molecular motor transport. We determined spatial distributions of motors in such organelles, corresponding to a basic scenario when motors only walk along the substrate, bind, unbind, and diffuse. We developed a mean-field model, which quantitatively reproduces elaborate stochastic simulation results as well as provides a physical interpretation of experimentally observed distributions of Myosin IIIa in stereocilia and filopodia. The mean-field model showed that the jamming of the walking motors is conspicuous, and therefore damps the active motor flux. However, when the motor distributions are coupled to the delivery of actin monomers toward the tip, even the concentration bump of G actin that they create before they jam is enough to speed up the diffusion to allow for severalfold longer filopodia. We found that the concentration profile of G actin along the filopodium is rather nontrivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this nonmonotonous shape is expected to occur under a broad set of conditions. We also find that the stationary motor distribution is universal for the given set of model parameters regardless of the organelle length, which follows from the form of the kinetic equations and the boundary conditions. M olecular motor transport in a living cell is one of the most fascinating processes in cellular biophysics. Molecular motors play crucial roles in many elongated organelles, such as neuronal axons (1), flagella (2), filopodia (3), stereocilia (4, 5), and microvilli (4). A naive view of cellular motor transport is that of motor molecules orderly following each other on the substrate and carrying cargo, which they unload at a destination point. However, in reality, motors not only walk, but also diffuse around the cell, randomly binding and unbinding to their substrate filaments and/or cargo. To a large extent these processes are governed by molecular noise. To understand how the motors perform their functions-be it cargo delivery to the growing end of an organelle or creating stresses in a flagellum, or even in artificial systems (6, 7)-it is necessary to know their spatial distribution in these systems.The spatial distribution of the motors could influence the delivery of building material toward the growing end of a dynamic elongated organelle, such as a filopodium or a stereocilium. In the absence of motors, the length of such organelle is expected to be limited by the slow diffusional delivery of the material to the tip (8). Furthermore, prior computational modeling of simple, conveyor-belt-like transport of monomeric species by molecular motors indicated that specially designed cooperative mechanisms are needed to achieve any appreciable active transport flux (9). Two main reasons for the transport inefficiency are sequestration of cargo by motors and diminution of motor speeds due to clogging of the filamentous bundle by walking mo...

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Myosin-X: a molecular motor at the cell's fingertips

Cited by 113 publications

References 73 publications

Comparative Maps of Motion and Assembly of Filamentous Actin and Myosin II in Migrating Cells

Comparative Maps of Motion and Assembly of Filamentous Actin and Myosin II in Migrating Cells

Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles

Theory of active transport in filopodia and stereocilia

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