Vertebrate Nonmuscle Myosin II Isoforms Rescue Small Interfering RNA-induced Defects in COS-7 Cell Cytokinesis

Bao, Jianjun; Jana, Siddhartha S.; Adelstein, Robert S.

doi:10.1074/jbc.m501573200

Cited by 106 publications

(130 citation statements)

References 33 publications

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“…Collectively, these results demonstrated that MYH10 was involved in the switch from mitosis to endomitosis. This result is in agreement with previous results that have shown that MYH10 is involved in cytokinesis and that its knockdown in cell lines leads to multinucleated polyploid cells 15,20,21 .…”

Section: Myh10 Is Involved In the Switch From Mitosis To Endomitosissupporting

confidence: 94%

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RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

et al. 2012

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megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis) during differentiation, leading to an increase in cell size and protein production that precedes platelet production. Recent evidence demonstrates that endomitosis is a consequence of a late failure in cytokinesis associated with a contractile ring defect. Here we show that the non-muscle myosin IIB heavy chain (mYH10) is expressed in immature megakaryocytes and specifically localizes in the contractile ring. mYH10 downmodulation by short hairpin RnA increases polyploidization by inhibiting the return of 4n cells to 2n, but other regulators, such as of the G1/s transition, might regulate further polyploidization of the 4n cells. Conversely, re-expression of mYH10 in the megakaryocytes prevents polyploidization and the transition of 2n to 4n cells. During polyploidization, mYH10 expression is repressed by the major megakaryocyte transcription factor RunX1. Thus, RunX1-mediated silencing of mYH10 is required for the switch from mitosis to endomitosis, linking polyploidization with megakaryocyte differentiation.

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Section: Myh10 Is Involved In the Switch From Mitosis To Endomitosissupporting

confidence: 94%

“…However, MYH10 silencing does not explain the entire polyploidization process. MYH10 silencing has a central role at the 2N-4N transition in MK by inducing failure of cytokinesis as also observed in MYH10-ablated cardiac myocytes 21 or COS cells 15,20 . However, MKs are not subsequently blocked in 4N.…”

Section: Discussionmentioning

confidence: 59%

RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

et al. 2012

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“…The defect may be accompanied by an obstructed aqueduct of Sylvius, the narrow channel connecting the third and fourth brain ventricles (noncommunicating hydrocephalus), or by a normal aqueduct (communicating hydrocephalus). The pathogenesis of most cases of communicating hydrocephalus is largely unknown (for reviews, see Perez-Figares et al, 2001;Crews et al, 2004).Nonmuscle myosin (NM) II, one of the major cytoskeletal motor proteins, plays an important role in cell migration (Svitkina et al, 1997;Ma et al, 2004;Even-Ram et al, 2007;Vicente-Manzanares et al, 2007), cell-cell adhesion Shewan et al, 2005;Giannone et al, 2007), and cell division (De Lozanne and Spudich, 1987;Takeda et al, 2003;Bao et al, 2005). The molecular structure of NM II is a hexamer consisting of a pair of myosin heavy chains (200 kDa) and two pairs of light chains (20 and 17 kDa).…”

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confidence: 99%

Loss of Cell Adhesion Causes Hydrocephalus in Nonmuscle Myosin II-B–ablated and Mutated Mice

Bao

Adelstein

2007

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102

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Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads to marked enlargement of the cerebral ventricles and destruction of brain tissue, due to hydrocephalus. We have identified a transient mesh-like structure present at the apical border of cells lining the spinal canal of mice during development. This structure, which only contains the II-B isoform of NM, also contains ␤-catenin and N-cadherin, consistent with a role in cell adhesion. Ablation of NM II-B or replacement of NM II-B with decreased amounts of a mutant (R709C), motor-impaired NM II-B in mice results in collapse of the mesh-like structure and loss of cell adhesion. This permits the underlying neuroepithelial cells to invade the spinal canal and obstruct cerebral spinal fluid flow. These defects in the CNS of NM II-B-ablated mice seem to be the cause of hydrocephalus. Interestingly, the mesh-like structure and patency of the spinal canal can be restored by increasing expression of the motor-impaired NM II-B, which also rescues hydrocephalus. However, the mutant isoform cannot completely rescue neuronal cell migration. These studies show that the scaffolding properties of NM II-B play an important role in cell adhesion, thereby preventing hydrocephalus during mouse brain development. INTRODUCTIONCongenital hydrocephalus affects one to three humans per 1000 live births. The results of this abnormality can be devastating in that severe, untreated hydrocephalus can destroy brain tissue and thereby lead to mental retardation. Hydrocephalus occurs when there is an increase in pressure in the ventricular chambers due to a blockage in the circulation of cerebral spinal fluid (CSF) or when there is an increase in production or decrease in the absorption of the CSF. The defect may be accompanied by an obstructed aqueduct of Sylvius, the narrow channel connecting the third and fourth brain ventricles (noncommunicating hydrocephalus), or by a normal aqueduct (communicating hydrocephalus). The pathogenesis of most cases of communicating hydrocephalus is largely unknown (for reviews, see Perez-Figares et al., 2001;Crews et al., 2004).Nonmuscle myosin (NM) II, one of the major cytoskeletal motor proteins, plays an important role in cell migration (Svitkina et al., 1997;Ma et al., 2004;Even-Ram et al., 2007;Vicente-Manzanares et al., 2007), cell-cell adhesion Shewan et al., 2005;Giannone et al., 2007), and cell division (De Lozanne and Spudich, 1987;Takeda et al., 2003;Bao et al., 2005). The molecular structure of NM II is a hexamer consisting of a pair of myosin heavy chains (200 kDa) and two pairs of light chains (20 and 17 kDa). In mammals, three isoforms of the nonmuscle myosin heavy chain (NMHC) have been identified, NMHC II-A, II-B, and II-C, encoded by three different genes, Myh 9, Myh 10, and Myh 14 in humans. The NMHCs share a 60 -80% identity in amino acids, but they show significant differences in their motor activities (Golomb et al., 2004;Kim et al., 2005). In general, all three isoforms are ubiquitously expressed in vertebrat...

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“…For example, M2B is highly expressed in non-vascular brain tissue, but is absent from many blood components, including lymphocytes, thymocytes and platelets. M2A is plentiful in leucocytes and organs rich in smooth muscle yet is minimal in many other tissues and absent from some cell lines, such as monkey COS-7 cells (Bao et al 2005). M2C message is low in fetal tissues in comparison to M2A and M2B mRNA (Golomb et al 2004).…”

Section: Localisation Expression Development Diseasementioning

confidence: 99%

“…For example, in cardiac myocytes (which lack M2A), complete ablation of M2B results in cell enlargement and binucleation, yet the presence of M2B at only 6% of wild-type levels confers normal phenotype (Takeda et al 2003). Further, in monkey COS-7 cells (which also lack M2A), knockdown of M2B significantly inhibited cell proliferation and led to the generation of multi-nucleated cells (Bao et al 2005), a situation rescued by exogenous M2A or M2C, but not by the less abundant endogenous M2C. This demonstrates that functional redundancy can occur between myosin 2 isoforms in some situations.…”

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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Vertebrate Nonmuscle Myosin II Isoforms Rescue Small Interfering RNA-induced Defects in COS-7 Cell Cytokinesis

Cited by 106 publications

References 33 publications

RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

Loss of Cell Adhesion Causes Hydrocephalus in Nonmuscle Myosin II-B–ablated and Mutated Mice

Conventional myosins – unconventional functions

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