A Specific Isoform of Nonmuscle Myosin II-C Is Required for Cytokinesis in a Tumor Cell Line

Jana, Siddhartha S.; Kawamoto, Sachiyo; Adelstein, Robert S.

doi:10.1074/jbc.m604606200

Cited by 56 publications

(63 citation statements)

References 38 publications

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“…Furthermore NMII-A and NMII-B have an opposing effect on motility, since depletion of NMII-A leads to increased motility while NMII-B depletion hinders motility (21,22). NMII-C plays a role in cytokinesis (23) and has distinct distribution in neuronal cells (24). Furthermore one NMII isoform only partly rescue cells in which siRNA was used to reduce the expression of another isoform (23,25).…”

Section: Non Muscle Myosin II (Nmii)mentioning

confidence: 99%

“…NMII-C plays a role in cytokinesis (23) and has distinct distribution in neuronal cells (24). Furthermore one NMII isoform only partly rescue cells in which siRNA was used to reduce the expression of another isoform (23,25). This functional diversity is achieved despite a significant amino acid sequence identity between the isoforms (overall 64 -80%), and the origin of these differential distributions and functions is not completely understood.…”

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confidence: 99%

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Myosin II Tailpiece Determines Its Paracrystal Structure, Filament Assembly Properties, and Cellular Localization

Rönen¹,

Ravid²

2009

Journal of Biological Chemistry

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Non muscle myosin II (NMII) is a major motor protein present in all cell types. The three known vertebrate NMII isoforms share high sequence homology but play different cellular roles. The main difference in sequence resides in the C-terminal nonhelical tailpiece (tailpiece). In this study we demonstrate that the tailpiece is crucial for proper filament size, overcoming the intrinsic properties of the coiled-coil rod. Furthermore, we show that the tailpiece by itself determines the NMII filament structure in an isoform-specific manner, thus providing a possible mechanism by which each NMII isoform carries out its unique cellular functions. We further show that the tailpiece determines the cellular localization of NMII-A and NMII-B and is important for NMII-C role in focal adhesion complexes. We mapped NMII-C sites phosphorylated by protein kinase C and casein kinase II and showed that these phosphorylations affect its solubility properties and cellular localization. Thus phosphorylation fine-tunes the tailpiece effects on the coiled-coil rod, enabling dynamic regulation of NMII-C assembly. We thus show that the small tailpiece of NMII is a distinct domain playing a role in isoform-specific filament assembly and cellular functions. Non muscle myosin II (NMII)2 is a major motor protein present in all cell types participating in crucial processes, including cytokinesis, surface attachment, and cell movement (1-3). NMII units are hexamers of two long heavy chains with two pairs of light chains attached. NMII heavy chain is composed of a globular head containing the actin binding and force generating ATPase domains, followed by a large coiled-coil rod that terminates with a short non-helical tailpiece (tailpiece). To carry out its cellular functions, NMII assembles into dimers and higher order filaments by interactions of the coiled-coil rod (4). The assembly process is governed by electrostatic interactions between adjacent coiled-coil rods containing alternating charged regions with specific periodicity (5-9) and is enhanced by activation of the motor domain through regulatory light chain phosphorylation (10 -12). The charge periodicity also determines the register and orientation of each NMII hexamer in the filament. Additionally the C-terminal region of the coiled-coil rod contains a distinctive positively charged region and the assembly-competence domains that are crucial for proper filament assembly (5-9, 13).Three isoforms of NMII (termed NMII-A, NMII-B, and NMII-C) have been identified in mammals (14 -16). Although NMII isoforms share somewhat overlapping roles, each isoform has distinctive tissue distribution and specific functions. NMII-A is important for neural growth cone retraction (17,18) and is distributed to the front of migrating endothelial cells (19). While NMII-B participates in growth cone advancement (20) and was detected in the retracting tails of migrating endothelial cells (19). Furthermore NMII-A and NMII-B have an opposing effect on motility, since depletion of NMII-A leads to increased mot...

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Section: Non Muscle Myosin II (Nmii)mentioning

confidence: 99%

mentioning

confidence: 99%

Myosin II Tailpiece Determines Its Paracrystal Structure, Filament Assembly Properties, and Cellular Localization

Rönen¹,

Ravid²

2009

Journal of Biological Chemistry

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“…Several studies have identified differences in mRNA expression, protein localization, enzymatic properties of the motor domain and binding partners between the three myosin II isoforms. [12][13][14][15][16][17][18][19][20] Accordingly, mouse knockouts for nonmuscle myosins IIA and IIB show distinct phenotypes. 21,22 In mammalian cells, phosphorylation of the regulatory light chains is the predominant mechanism regulating myosin II activity.…”

Section: Introductionmentioning

confidence: 99%

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Clark

Middelbeek

Lasonder

et al. 2008

Journal of Molecular Biology

123

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Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca 2+ -and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOHtermini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

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“…The B2 isoform, possessing a 21 amino acid insert near the actin-binding region, is required for the postnatal development of cerebellar Purkinje cells (Ma et al 2006) yet, for example, is not expressed in neurons of the olfactory lobe (Takahashi et al 1999). While developmental roles for the inserted isoforms of M2C remain unclear, the C1 insert, consisting of 8 amino acids and found within the myosin head on the analogous loop to that of B1, has been shown to be required for cytokinesis in a human lung tumour cell line (Jana et al 2006). …”

Section: Localisation Expression Development Diseasementioning

confidence: 99%

“…Note that normal cell phenotype (a) is altered upon depletion of M2C causing an increase in cell body diameter and profuse vacuolisation (b); this aberrant phenotype is reversed following a 72-h recovery period in the absence of oligonucleotide (c). Scale bar 60 μm A549 lung carcinoma cells, which possess all three isoforms, exhibited slow proliferation in response to knockdown of the C1 inserted isoform of M2C (Jana et al 2006), a situation that could not be rescued by application of exogenous M2A or M2B. The C1 isoform was localised, during cell division, to the intercellular bridge linking dividing cells.…”

Section: Cytokinesismentioning

confidence: 99%

Conventional myosins – unconventional functions

et al. 2010

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While the discovery of unconventional myosins raised expectations that their actions were responsible for most aspects of actin-based cell motility, few anticipated the wide range of cellular functions that would remain the purview of conventional two-headed myosins. The three nonsarcomeric, cellular myosins-M2A, M2B and M2C-participate in diverse roles including, but not limited to: neuronal dynamics, axon guidance and synaptic transmission; endothelial cell migration; cell adhesion, polarity, fusion and cytokinesis; vesicle trafficking and viral egress. These three conventional myosins each take on specific, differing functional roles during development and maturity, characteristic of each cell lineage; exact roles depend on the developmental stage of the cell, cellular location, upstream regulatory controls, relative isoform expression, orientation and associated state of the actin cytoscaffolds in which these myosins operate. Here, we discuss the separate yet related roles that characterise the actions of M2A, M2B and M2C in various cell types and show that these conventional myosins are responsible for functions as unconventional as any performed by unconventional myosins.

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A Specific Isoform of Nonmuscle Myosin II-C Is Required for Cytokinesis in a Tumor Cell Line

Cited by 56 publications

References 38 publications

Myosin II Tailpiece Determines Its Paracrystal Structure, Filament Assembly Properties, and Cellular Localization

Myosin II Tailpiece Determines Its Paracrystal Structure, Filament Assembly Properties, and Cellular Localization

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Conventional myosins – unconventional functions

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