A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion
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 fusio...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/51358 |
| _version_ | 1811227614030856192 |
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| author | Ka Man Carmen Chan Sungmin Son Eva M Schmid Daniel A Fletcher |
| author_facet | Ka Man Carmen Chan Sungmin Son Eva M Schmid Daniel A Fletcher |
| author_sort | Ka Man Carmen Chan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:43:57Z |
| format | Article |
| id | doaj.art-0e4491b654a24d09b2326ed3b5d4d665 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:43:57Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0e4491b654a24d09b2326ed3b5d4d6652022-12-22T03:37:59ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.51358A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusionKa Man Carmen Chan0https://orcid.org/0000-0002-8595-9725Sungmin Son1Eva M Schmid2Daniel A Fletcher3https://orcid.org/0000-0002-1890-5364UC Berkeley–UC San Francisco Graduate Group in Bioengineering, Berkeley, United States; Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United StatesDepartment of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United StatesDepartment of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United StatesUC Berkeley–UC San Francisco Graduate Group in Bioengineering, Berkeley, United States; Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States; Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, United States; Chan Zuckerberg Biohub, San Francisco, United StatesCell-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.https://elifesciences.org/articles/51358cell fusionactin cytoskeletonhost-pathogen interactions |
| spellingShingle | Ka Man Carmen Chan Sungmin Son Eva M Schmid Daniel A Fletcher A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion eLife cell fusion actin cytoskeleton host-pathogen interactions |
| title | A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion |
| title_full | A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion |
| title_fullStr | A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion |
| title_full_unstemmed | A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion |
| title_short | A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion |
| title_sort | viral fusogen hijacks the actin cytoskeleton to drive cell cell fusion |
| topic | cell fusion actin cytoskeleton host-pathogen interactions |
| url | https://elifesciences.org/articles/51358 |
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