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

Ka Man Carmen Chan, Sungmin Son, Eva M. Schmid, View ORCID ProfileDaniel A. Fletcher
doi: https://doi.org/10.1101/761502
Ka Man Carmen Chan
1UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA 94720, USA
2Department of Bioengineering & Biophysics Group, University of California, Berkeley, Berkeley, CA 94720, USA
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Sungmin Son
2Department of Bioengineering & Biophysics Group, University of California, Berkeley, Berkeley, CA 94720, USA
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Eva M. Schmid
2Department of Bioengineering & Biophysics Group, University of California, Berkeley, Berkeley, CA 94720, USA
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Daniel A. Fletcher
1UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA 94720, USA
2Department of Bioengineering & Biophysics Group, University of California, Berkeley, Berkeley, CA 94720, USA
3Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
4Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
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  • ORCID record for Daniel A. Fletcher
  • For correspondence: fletch@berkeley.edu
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Abstract

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 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 Statement A viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 08, 2019.
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A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion
Ka Man Carmen Chan, Sungmin Son, Eva M. Schmid, Daniel A. Fletcher
bioRxiv 761502; doi: https://doi.org/10.1101/761502
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A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion
Ka Man Carmen Chan, Sungmin Son, Eva M. Schmid, Daniel A. Fletcher
bioRxiv 761502; doi: https://doi.org/10.1101/761502

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