scholarly journals YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniel Feliciano ◽  
Carolyn M. Ott ◽  
Isabel Espinosa-Medina ◽  
Aubrey V. Weigel ◽  
Lorena Benedetti ◽  
...  

AbstractCells in many tissues, such as bone, muscle, and placenta, fuse into syncytia to acquire new functions and transcriptional programs. While it is known that fused cells are specialized, it is unclear whether cell-fusion itself contributes to programmatic-changes that generate the new cellular state. Here, we address this by employing a fusogen-mediated, cell-fusion system to create syncytia from undifferentiated cells. RNA-Seq analysis reveals VSV-G-induced cell fusion precedes transcriptional changes. To gain mechanistic insights, we measure the plasma membrane surface area after cell-fusion and observe it diminishes through increases in endocytosis. Consequently, glucose transporters internalize, and cytoplasmic glucose and ATP transiently decrease. This reduced energetic state activates AMPK, which inhibits YAP1, causing transcriptional-reprogramming and cell-cycle arrest. Impairing either endocytosis or AMPK activity prevents YAP1 inhibition and cell-cycle arrest after fusion. Together, these data demonstrate plasma membrane diminishment upon cell-fusion causes transient nutrient stress that may promote transcriptional-reprogramming independent from extrinsic cues.

2019 ◽  
Author(s):  
Daniel Feliciano ◽  
Isabel Espinosa-Medina ◽  
Aubrey Weigel ◽  
Kristin M. Milano ◽  
Zhonghua Tang ◽  
...  

SummaryDeveloping cells divide and differentiate, and in many tissues, such as bone, muscle, and placenta, cells fuse acquiring specialized functions. While it is known that fused-cells are differentiated, it is unclear what mechanisms trigger the programmatic-change, and whether cell-fusion alone drives differentiation. To address this, we employed a fusogen-mediated cell-fusion system involving undifferentiated cells in tissue culture. RNA-seq analysis revealed cell-fusion initiates a dramatic transcriptional change towards differentiation. Dissecting the mechanisms causing this reprogramming, we observed that after cell-fusion plasma-membrane surface area decreases through increased endocytosis. Consequently, glucose-transporters are internalized, and cytoplasmic-glucose and ATP transiently decrease. This low-energetic state activates AMPK, which inhibits YAP1, causing cell-cycle arrest. Impairing either endocytosis or AMPK prevents YAP1 inhibition and cell-cycle arrest after fusion. Together these data suggest that cell-fusion-induced differentiation does not need to rely on extrinsic-cues; rather the plasma-membrane diminishment forced by the geometric-transformations of cell-fusion cause transient cell-starvation that induces differentiation.


2016 ◽  
Vol 34 (1) ◽  
pp. 127-138 ◽  
Author(s):  
Shigeki Sugawara ◽  
Changhun Im ◽  
Tasuku Kawano ◽  
Takeo Tatsuta ◽  
Yasuhiro Koide ◽  
...  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Paola Bardetti ◽  
Sónia Marisa Castanheira ◽  
Oliver Valerius ◽  
Gerhard H Braus ◽  
José Pérez-Martín

In the fungus Ustilago maydis, sexual pheromones elicit mating resulting in an infective filament able to infect corn plants. Along this process a G2 cell cycle arrest is mandatory. Such as cell cycle arrest is initiated upon the pheromone recognition in each mating partner, and sustained once cell fusion occurred until the fungus enter the plant tissue. We describe that the initial cell cycle arrest resulted from inhibition of the nuclear transport of the mitotic inducer Cdc25 by targeting its importin, Kap123. Near cell fusion to take place, the increase on pheromone signaling promotes Cdc25 degradation, which seems to be important to ensure the maintenance of the G2 cell cycle arrest to lead the formation of the infective filament. This way, premating cell cycle arrest is linked to the subsequent steps required for establishment of the infection. Disabling this connection resulted in the inability of fungal cells to infect plants.


2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Gerhard ◽  
C Schmees ◽  
R Rad ◽  
P Voland ◽  
T Treptau ◽  
...  

10.2741/a527 ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. d479-487 ◽  
Author(s):  
Dan Grandér

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