TY - JOUR
T1 - Cytoskeleton reorganization in influenza hemagglutinin-initiated syncytium formation
AU - Richard, Jean Philippe
AU - Leikina, Eugenia
AU - Chernomordik, Leonid V.
N1 - Funding Information:
We thank A. Bershadsky, A. Chen, L. Joubert-Mang, M. Kozlov, B. Lebleu, K. Melikov, B. Podbilewicz, E. Zaitseva, and J. Zimmerberg for very helpful discussions. This research was supported by the Intramural Research Program of the NIH, NICHD.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Cytoskeleton
KW - Influenza hemagglutinin
KW - Membrane fusion
KW - Syncytium
UR - http://www.scopus.com/inward/record.url?scp=59249104008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59249104008&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2008.09.014
DO - 10.1016/j.bbamem.2008.09.014
M3 - Article
C2 - 18976631
AN - SCOPUS:59249104008
SN - 0005-2736
VL - 1788
SP - 450
EP - 457
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 2
ER -