Cytoskeleton reorganization in influenza hemagglutinin-initiated syncytium formation.
Little is known about the mechanisms of cell-cell fusion in development and diseases and, especially, about fusion stages downstream of an opening of nascent fusion pore(s). Earlier works on different cell-cell fusion reactions have indicated that cytoskeleton plays important role in syncytium formation. However, due to complexity of these reactions and multifaceted contributions of cytoskeleton in cell physiology, it has remained unclear whether cytoskeleton directly drives fusion pore expansion or affects preceding fusion stages. Here we explore cellular reorganization associated with fusion pore expansion in syncytium formation using relatively simple experimental system. Fusion between murine embryonic fibroblasts NIH3T3-based cells is initiated on demand by well-characterized fusogen influenza virus hemagglutinin. We uncouple early fusion stages dependent on protein fusogens from subsequent fusion pore expansion stage and establish that the transition from local fusion to syncytium requires metabolic activity of living cells. Effective syncytium formation for cells with disorganized actin and microtubule cytoskeleton argues against hypothesis that cytoskeleton drives fusion expansion.
Richard
Jean-Philippe
JP
Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
Leikina
Eugenia
E
Chernomordik
Leonid V
LV
D000199:Actins / Q000378:metabolism; D000818:Animals; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D041681:NIH 3T3 Cells
D000199:Actins; D019267:Hemagglutinin Glycoproteins, Influenza Virus