Changes in cytoskeletal organization in polyoma middle T antigen-transformed fibroblasts: Involvement of protein phosphatase 2A andsrc tyrosine kinases

Costa, Silvia R. da; Wang, Y; Vilalta, Patricia M.; Schönthal, Axel H.

doi:10.1002/1097-0169(200012)47:4<253::aid-cm1>3.0.co;2-s

Cited by 5 publications

(6 citation statements)

References 53 publications

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“…Disturbance of one component of the cytoskeletal network leads to changes of other components. Middle T antigen of MPyV is able to deplete acetylation of microtubules and mediate loss of focal adhesions and actin stress fibers [47]. Rathje et al [45] demonstrated that cells constitutively expressing LT antigen of SV40 exhibited reorganization of vimentin filaments (belonging to intermediate filament family) and also that expression of LT decreased the level of a-tubulin acetylation.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, small T (sT) antigen of Merkel cell polyomavirus promotes lowered a-tubulin acetylation and mediates microtubule destabilization leading to increased cellular motility and migration [46]. Middle T antigen of MPyV is able to deplete acetylation of microtubules and mediate loss of focal adhesions and actin stress fibers [47]. VP1 fibers might compensate for the loss of one cytoskeletal network component by strengthening another and thus maintain the cell shape, having thus an opposite effect to T antigens.…”

Section: Discussionmentioning

confidence: 99%

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VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle

et al. 2017

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VP1, the major structural protein of the mouse polyomavirus (MPyV), is the major architectural component of the viral capsid. Its pentamers are able to self-assemble into capsid-like particles and to non-specifically bind DNA. Surface loops of the protein interact with sialic acid of ganglioside receptors. Although the replication cycle of the virus, including virion morphogenesis, proceeds in the cell nucleus, a substantial fraction of the protein is detected in the cytoplasm of late-phase MPyV-infected cells. In this work, we detected VP1 mainly in the cytoplasm of mammalian cells transfected with plasmid expressing VP1. In the cytoplasm, VP1-bound microtubules, including the mitotic spindle, and the interaction of VP1 with microtubules resulted in cell cycle block at the G2/M phase. Furthermore, in the late phase of MPyV infection and in cells expressing VP1, microtubules were found to be hyperacetylated. We then sought to understand how VP1 interacts with microtubules. Dynein is not responsible for the VP1-microtubule association, as neither overexpression of p53/dynamitin nor treatment with ciliobrevin-D (an inhibitor of dynein activity) prevented binding of VP1 to microtubules. A pull-down assay for VP1-interacting proteins identified the heat shock protein 90 (Hsp90) chaperone, and Hsp90 was also detected in the VP1-microtubule complexes. Although Hsp90 is known to be associated with acetylated microtubules, it does not mediate the interaction between VP1 and microtubules. Our study provides insight into the role of the major structural protein in MPyV replication, indicating that VP1 is a multifunctional protein that participates in the regulation of cell cycle progression in MPyV-infected cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle

et al. 2017

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“…Cells grown on 100 mm Petri dishes were stimulated with either vehicle (media) or thrombin. Separation of MT-enriched, cytoskeletal (CSK), and cytosolic (CSL) fractions was performed as described elsewhere (33). Supernatants containing cytosolic proteins and pellets containing particulate fraction were solubilized in 3ϫ SDS sample buffer; specific protein content in cytosolic and particulate fractions was analyzed by Western immunoblotting.…”

Section: Isolation Of Microtubules and Mapsmentioning

confidence: 99%

Novel role of microtubules in thrombin‐induced endothelial barrier dysfunction

et al. 2004

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Disturbances in endothelial cell (EC) barrier regulation are critically dependent upon rearrangements of EC actin cytoskeleton. However, the role of microtubule (MT) network in the regulation of EC permeability is not well understood. We examined involvement of MT remodeling in thrombin-induced EC permeability and explored MT regulation by heterotrimeric G12/13 proteins and by small GTPase Rho. Thrombin induced phosphorylation of MT regulatory protein tau at Ser409 and Ser262 and peripheral MT disassembly, which was linked to increased EC permeability. MT stabilization by taxol attenuated thrombin-induced permeability, actin remodeling, and paracellular gap formation and diminished thrombin-induced activation of Rho and Rho-kinase. Expression of activated Galpha12/13 subunits involved in thrombin-mediated signaling or their effector p115RhoGEF involved in Rho activation caused MT disassembly, whereas p115RhoGEF-specific negative regulator RGS preserved MT from thrombin-induced disassembly. Consistent with these results, expression of activated RhoA and Rho-kinase induced MT disassembly. Conversely, thrombin-induced disassembly of peripheral MT network was attenuated by expression of dominant negative RhoA and Rho-kinase mutants or by pharmacological inhibition of Rho-kinase. Collectively, our data demonstrate for the first time a critical involvement of MT disassembly in thrombin-induced EC barrier dysfunction and indicate G-protein-dependent mechanisms of thrombin-induced MT alteration.

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“…In MT-expressing cells, a pool of stable microtubules was depleted, and the association of PP2A with microtubules and PP2A activity was increased. In addition, MT reduced the number of focal adhesions and actin stress fibers, which was accompanied by the redistribution of another MT-interacting protein, SRC protein kinase [96]. The regulation of the microtubule array by MT is caused by the direct effect of PP2A redistribution, as well as indirectly, by the reorganization of the actin cytoskeleton.…”

Section: Polyomavirus T Antigens Destabilize Microtubules To Induce Cmentioning

confidence: 95%

“…The expression of mouse polyomavirus middle T antigen was shown to affect microtubules' organization [96]. MT interacts with protein phosphatase PP2A [97] composed of three subunits, structural A, regulatory B, and catalytic C subunit [98].…”

Section: Polyomavirus T Antigens Destabilize Microtubules To Induce Cmentioning

confidence: 99%

Microtubules in Polyomavirus Infection

Horníková

Bruštíková

Forstová

2020

Viruses

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Microtubules, part of the cytoskeleton, are indispensable for intracellular movement, cell division, and maintaining cell shape and polarity. In addition, microtubules play an important role in viral infection. In this review, we summarize the role of the microtubules’ network during polyomavirus infection. Polyomaviruses usurp microtubules and their motors to travel via early and late acidic endosomes to the endoplasmic reticulum. As shown for SV40, kinesin-1 and microtubules are engaged in the release of partially disassembled virus from the endoplasmic reticulum to the cytosol, and dynein apparently assists in the further disassembly of virions prior to their translocation to the cell nucleus—the place of their replication. Polyomavirus gene products affect the regulation of microtubule dynamics. Early T antigens destabilize microtubules and cause aberrant mitosis. The role of these activities in tumorigenesis has been documented. However, its importance for productive infection remains elusive. On the other hand, in the late phase of infection, the major capsid protein, VP1, of the mouse polyomavirus, counteracts T-antigen-induced destabilization. It physically binds microtubules and stabilizes them. The interaction results in the G2/M block of the cell cycle and prolonged S phase, which is apparently required for successful completion of the viral replication cycle.

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Changes in cytoskeletal organization in polyoma middle T antigen-transformed fibroblasts: Involvement of protein phosphatase 2A andsrc tyrosine kinases

Cited by 5 publications

References 53 publications

VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle

VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle

Novel role of microtubules in thrombin‐induced endothelial barrier dysfunction

Microtubules in Polyomavirus Infection

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