Controlled plasmonic cell fusion and its implications on the actin cytoskeleton (Conference Presentation)

2020 ◽  
Author(s):  
Julia Belansky ◽  
Limor Minai ◽  
Dvir Yelin
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Fusion

Cell fusion mediates dramatic alterations in the actin cytoskeleton, focal adhesions, and E-cadherin in trophoblastic cells

Cytoskeleton ◽  
2014 ◽  
Vol 71 (4) ◽  
pp. 241-256 ◽  
Author(s):  
Atsuko Ishikawa ◽  
Waka Omata ◽  
William E. Ackerman ◽  
Toshiyuki Takeshita ◽  
Dale D. Vandré ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Focal Adhesions ◽  
Trophoblastic Cells ◽  
E Cadherin

scholarly journals The Cell Wall Integrity MAPK pathway controls actin cytoskeleton assembly during fungal somatic cell fusion

2020 ◽  
Author(s):  
Antonio Serrano ◽  
Hamzeh H. Hammadeh ◽  
Natalie Schwarz ◽  
Ulrike Brandt ◽  
André Fleißner
Keyword(s):  
Cell Wall ◽  
Actin Cytoskeleton ◽  
Somatic Cell ◽  
Cell Fusion ◽  
Rho Gtpase ◽  
Cell Wall Integrity ◽  
Physical Contact ◽  
Functional Link ◽  
Somatic Cell Fusion ◽  
Gtpase Rac

AbstractSomatic cell fusion is widely studied in the filamentous fungus Neurospora crassa. The interaction of genetically identical germlings is mediated by a signaling mechanism in which the cells take turns in signal-sending and receiving. The switch between these physiological states is represented by the alternating membrane recruitment of the SO protein and the MAPK MAK-2. This dialog-like behavior is observed until the cells establish physical contact, when the cell-wall-integrity MAK-1 is recruited to the contact area to control the final steps of the cell fusion process. This work revealed, for the first-time, an additional MAK-1-function during the tropic growth phase. Specific inhibition of MAK-1 during tropic-growth resulted in disassembly of the actin-aster, and mislocalization of SO and MAK-2. Similar defects were observed after the inhibition of the Rho-GTPase RAC-1, suggesting a functional link between them, being MAK-1 upstream of RAC-1. In contrast, after inhibition of MAK-2, the actin-aster stayed intact, however, its subcellular localization became instable within the cell-membrane. Together these observations led to a new working model, in which MAK-1 promotes the formation and stability of the actin-aster, while MAK-2 controls its positionning and cell growth directionality.Summary statementThe CWI MAPK MAK-1 pathway controls actin cytoskeleton assembly at the cell tips through activation of the Rho-GTPase RAC-1 exclusively on somatic cell fusion.

scholarly journals Evolutionarily related small viral fusogens hijack distinct but modular actin nucleation pathways to drive cell-cell fusion

2020 ◽  
Vol 118 (1) ◽  
pp. e2007526118
Author(s):  
Ka Man Carmen Chan ◽  
Ashley L. Arthur ◽  
Johannes Morstein ◽  
Meiyan Jin ◽  
Abrar Bhat ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Conformational Changes ◽  
Binding Motif ◽  
Mechanical Pressure ◽  
Actin Nucleation ◽  
Viral Spread ◽  
Fast Proteins ◽  
Cell Cell

Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP–mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.

scholarly journals A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ka Man Carmen Chan ◽  
Sungmin Son ◽  
Eva M Schmid ◽  
Daniel A Fletcher
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Conformational Changes ◽  
Close Contact ◽  
Adaptor Protein ◽  
Cytoplasmic Domain ◽  
Actin Assembly ◽  
Actin Network ◽  
Cell Cell

Cell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that phosphorylation of the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network. Using p14 mutants, we demonstrate that fusion is abrogated when binding of an adaptor protein is prevented and that direct coupling of the fusogenic ectodomain to branched actin assembly is sufficient to drive cell-cell fusion. This work reveals how the actin cytoskeleton can be harnessed to overcome energetic barriers to cell-cell fusion.

scholarly journals Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion

2010 ◽  
Vol 21 (22) ◽  
pp. 3973-3984 ◽  
Author(s):  
Yukinao Shibukawa ◽  
Natsuko Yamazaki ◽  
Keiichi Kumasawa ◽  
Etsuko Daimon ◽  
Michiko Tajiri ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Syncytium Formation ◽  
Terminal Region ◽  
Negative Regulator ◽  
Dominant Negative Effect ◽  
Bewo Cell ◽  
Phosphorylation Sites ◽  
Dependent Manner ◽  
Cytoskeleton Rearrangement

Cell–cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent.

scholarly journals The actin cytoskeleton inhibits pore expansion during PIV5 fusion protein-promoted cell–cell fusion

Virology ◽  
2010 ◽  
Vol 404 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Mark A. Wurth ◽  
Rachel M. Schowalter ◽  
Everett Clinton Smith ◽  
Carole L. Moncman ◽  
Rebecca Ellis Dutch ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Pore Expansion ◽  
Cell Cell

scholarly journals Spectraplakin Induces Positive Feedback between Fusogens and the Actin Cytoskeleton to Promote Cell-Cell Fusion

2017 ◽  
Vol 41 (1) ◽  
pp. 107-120.e4 ◽  
Author(s):  
Yihong Yang ◽  
Yan Zhang ◽  
Wen-Jun Li ◽  
Yuxiang Jiang ◽  
Zhiwen Zhu ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Positive Feedback ◽  
Cell Cell

scholarly journals A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion

2019 ◽  
Author(s):  
Ka Man Carmen Chan ◽  
Sungmin Son ◽  
Eva M. Schmid ◽  
Daniel A. Fletcher
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Conformational Changes ◽  
Close Contact ◽  
Cytoplasmic Domain ◽  
Force Generation ◽  
Actin Assembly ◽  
Actin Network ◽  
Cell Cell

AbstractCell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network, directly coupling local force generation with a short membrane-disruptive ectodomain. This work reveals that overcoming energetic barriers to cell-cell fusion does not require conformational changes of tall fusogens but can instead be driven by harnessing the host cytoskeleton.Impact StatementA viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.

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