RT Journal Article
SR Electronic
T1 A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 761502
DO 10.1101/761502
A1 Ka Man Carmen Chan
A1 Sungmin Son
A1 Eva M. Schmid
A1 Daniel A. Fletcher
YR 2019
UL http://biorxiv.org/content/early/2019/09/08/761502.abstract
AB 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.