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Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ

Devon E Mason, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin E Yoder, Joel D Boerckel
doi: https://doi.org/10.1101/265744
Devon E Mason
The University of Pennsylvania;
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James H Dawahare
The University of Notre Dame;
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Trung Dung Nguyen
The University of Notre Dame;
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Yang Lin
Indiana University;
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Sherry L. Voytik-Harbin
Purdue University
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Pinar Zorlutuna
The University of Notre Dame;
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Mervin E Yoder
Indiana University;
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Joel D Boerckel
The University of Pennsylvania;
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  • For correspondence: boerckel@pennmedicine.upenn.edu
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Abstract

Cell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whether de novo gene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix. The transcriptional co-activators YAP and TAZ mediate this feedback response, modulating cell mechanics by limiting cytoskeletal and focal adhesion maturation to enable persistent cell motility and 3D vasculogenesis. Motile arrest after YAP/TAZ ablation was rescued by depletion of the YAP/TAZ-dependent myosin phosphatase regulator, NUAK2, or by inhibition of Rho-ROCK-myosin II. Together, these data establish a transcriptional feedback axis necessary to maintain a responsive cytoskeletal equilibrium and enable neovascular function.

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The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC 4.0 International license.
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  • Posted February 15, 2018.

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Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ
Devon E Mason, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin E Yoder, Joel D Boerckel
bioRxiv 265744; doi: https://doi.org/10.1101/265744
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Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ
Devon E Mason, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin E Yoder, Joel D Boerckel
bioRxiv 265744; doi: https://doi.org/10.1101/265744

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