title: Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow.
abstract: Nonmuscle myosin IIA (NMM-IIA) is involved in the formation of focal adhesions and neurite retraction. However, the role of NMM-IIA in these functions remains largely unknown. Using RNA interference as a tool to decrease NMM-IIA expression, we have found that NMM-IIA is the major myosin involved in traction force generation and retrograde F-actin flow in mouse embryonic fibroblast cells. Quantitative analyses revealed that approximately 60% of traction force on fibronectin-coated surfaces is contributed by NMM-IIA and approximately 30% by NMM-IIB. The retrograde F-actin flow decreased dramatically in NMM-IIA-depleted cells, but seemed unaffected by NMM-IIB deletion. In addition, we found that depletion of NMM-IIA caused cells to spread at a higher rate and to a greater area on fibronectin substrates during the early spreading period, whereas deletion of NMM-IIB appeared to have no effect on spreading. The distribution of NMM-IIA was concentrated on the dorsal surface and approached the ventral surface in the periphery, whereas NMM-IIB was primarily concentrated around the nucleus and to a lesser extent at the ventral surface in cell periphery. Our results suggest that NMM-IIA is involved in generating a coherent cytoplasmic contractile force from one side of the cell to the other through the cross-linking and the contraction of dorsal actin filaments.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York, USA.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Cai
authors.forename: Nicolas
authors.initials: N
authors.lastname: Biais
authors.forename: Gregory
authors.initials: G
authors.lastname: Giannone
authors.forename: Monica
authors.initials: M
authors.lastname: Tanase
authors.forename: Guoying
authors.initials: G
authors.lastname: Jiang
authors.forename: Jake M
authors.initials: JM
authors.lastname: Hofman
authors.forename: Chris H
authors.initials: CH
authors.lastname: Wiggins
authors.forename: Pascal
authors.initials: P
authors.lastname: Silberzan
authors.forename: Axel
authors.initials: A
authors.lastname: Buguin
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D020409:Molecular Motor Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D024507:Nonmuscle Myosin Type IIA / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins; D024507:Nonmuscle Myosin Type IIA