Conventional myosins – unconventional functions

Chantler, Peter D.; Wylie, Steven R.; Wheeler‐Jones, Caroline P.D.; McGonnell, Imelda M.

doi:10.1007/s12551-010-0030-7

Cited by 12 publications

(9 citation statements)

References 125 publications

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“…The mammalian genome contains three genes encoding MHC isoforms, MHC IIA , MHC IIB , and MHC IIC , of which endothelial cells express the first two (56). We coimmunoprecipitated MHC IIA and MHC IIB, as well as the light chains MRLC and MELC, together with p75 Further studies are required to unravel the residues in myosin that are responsible for its binding to p75.…”

Section: Discussionmentioning

confidence: 99%

Release of Nonmuscle Myosin II from the Cytosolic Domain of Tumor Necrosis Factor Receptor 2 Is Required for Target Gene Expression

et al. 2013

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Tumor necrosis factor α (TNF-α) elicits its biological activities through activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as p75). The activities of both receptors are required for the TNF-α–induced proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is critical for either p55- or p75-mediated activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression. Here, we identified nonmuscle myosin II (myosin) as a binding partner of p75. TNF-α–dependent signaling by p75 and induction of target gene expression persisted for substantially longer in cells deficient in myosin regulatory light chain (MRLC, a component of myosin) than in cells replete in myosin. In resting endothelial cells, myosin was bound constitutively to the intracellular region of p75, a region that overlaps with the TRAF2-binding domain, and TNF-α caused the rapid dissociation of myosin from p75. At early time points after exposure to TNF-α, p75 activated Rho-associated kinase 1 (ROCK1). Inhibition of ROCK1 activity blocked TNF-α–dependent phosphorylation of MRLC and the dissociation of myosin from p75. ROCK1-dependent release of myosin was necessary for the TNF-α–dependent recruitment of TRAF2 to p75 and for p75-specific activation of NF-κB and MAPK signaling. Thus, our findings have revealed a previously uncharacterized, noncanonical regulatory function of myosin in cytokine signaling.

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Section: Discussionmentioning

confidence: 99%

Release of Nonmuscle Myosin II from the Cytosolic Domain of Tumor Necrosis Factor Receptor 2 Is Required for Target Gene Expression

et al. 2013

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“…These properties are already implemented by the vertebrate-specific myosin IIB ( Figure 3A ), a paralogue of the ancestrally derived myosin IIA ( Murakami et al. , 1998 , 2000 ; Chantler et al. , 2010 ; Stam et al.…”

Section: Thicker Stiffer Longer Fibrils Support Higher Force Producmentioning

confidence: 99%

Collagen, stiffness, and adhesion: the evolutionary basis of vertebrate mechanobiology

Tang

2020

MBoC

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The emergence of collagen I in vertebrates resulted in a dramatic increase in the stiffness of the extracellular environment, supporting long-range force propagation and the development of low-compliant tissues necessary for the development of vertebrate traits including pressurized circulation and renal filtration. Vertebrates have also evolved integrins that can bind to collagens, resulting in the generation of higher tension and more efficient force transmission in the extracellular matrix. The stiffer environment provides an opportunity for the vertebrates to create new structures such as the stress fibers, new cell types such as endothelial cells, new developmental processes such as neural crest delamination, and new tissue organizations such as the blood–brain barrier. Molecular players found only in vertebrates allow the modification of conserved mechanisms as well as the design of novel strategies that can better serve the physiological needs of the vertebrates. These innovations collectively contribute to novel morphogenetic behaviors and unprecedented increases in the complexities of tissue mechanics and functions.

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“…All myosin motor domains contain highly conserved residues that participate directly in actin and ATP binding, as well as ATP hydrolysis and force production (21,27). Previous studies established that mutations to these residues disrupt myosin activity in predictable ways (60)(61)(62)(63)(64).…”

Section: Nm2c Motor Domain Activity Is Required For Limiting Microvilmentioning

confidence: 99%

“…At higher levels of biological complexity, these motors have been implicated in shaping and bending of tissues, collective cell migration, and regulating the paracellular permeability of epithelial sheets (22,27). NM2 paralogs have distinct kinetic properties, which allow these motors to perform specific and distinct functions within the cell (28,29).…”

Section: Introductionmentioning

confidence: 99%

Non-muscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli

Chinowsky

Pinette

Meenderink

et al. 2020

Preprint

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Epithelial brush borders are large arrays of microvilli that enable efficient solute uptake from luminal spaces. In the context of the intestinal tract, brush border microvilli drive functions that are critical for physiological homeostasis, including nutrient uptake and host defense. However, cytoskeletal mechanisms that regulate the assembly and morphology of these protrusions are poorly understood. The parallel actin bundles that support microvilli have their pointed-end rootlets anchored in a highly crosslinked filamentous meshwork referred to as the "terminal web".Although classic EM studies revealed complex ultrastructure, the composition, organization, and function of the terminal web remains unclear. Here, we identify non-muscle myosin-2C (NM2C) as a major component of the brush border terminal web. NM2C is found in a dense, isotropic layer of puncta across the sub-apical domain, which transects the rootlets of microvillar actin bundles.Puncta in this network are separated by ~210 nm, dimensions that are comparable to the expected size of filaments formed by NM2C. In primary intestinal organoid cultures, the terminal web NM2C network is highly dynamic and exhibits continuous remodeling. Using pharmacological and genetic perturbations to disrupt NM2C activity in cultured intestinal epithelial cells, we found that this motor controls the length of growing microvilli by regulating actin turnover in a manner that requires a fully active motor domain. Our findings answer a decades old question on the function of terminal web myosin and hold broad implications for understanding apical morphogenesis in diverse epithelial systems.

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Conventional myosins – unconventional functions

Cited by 12 publications

References 125 publications

Release of Nonmuscle Myosin II from the Cytosolic Domain of Tumor Necrosis Factor Receptor 2 Is Required for Target Gene Expression

Release of Nonmuscle Myosin II from the Cytosolic Domain of Tumor Necrosis Factor Receptor 2 Is Required for Target Gene Expression

Collagen, stiffness, and adhesion: the evolutionary basis of vertebrate mechanobiology

Non-muscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli

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