Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion

N. O. Alieva, A. K. Efremov, S. Hu, D. Oh, Z. Chen, M. Natarajan, H. T. Ong, A. Jégou, G. Romet-Lemonne, J. T. Groves, M. P. Sheetz, J. Yan and A. D. Bershadsky ()
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N. O. Alieva: National University of Singapore, T-lab
A. K. Efremov: National University of Singapore, T-lab
S. Hu: National University of Singapore, T-lab
D. Oh: National University of Singapore, T-lab
Z. Chen: National University of Singapore, T-lab
M. Natarajan: National University of Singapore, T-lab
H. T. Ong: National University of Singapore, T-lab
A. Jégou: Institut Jacques Monod, CNRS, Université de Paris
G. Romet-Lemonne: Institut Jacques Monod, CNRS, Université de Paris
J. T. Groves: National University of Singapore, T-lab
M. P. Sheetz: National University of Singapore, T-lab
J. Yan: National University of Singapore, T-lab
A. D. Bershadsky: National University of Singapore, T-lab

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Filopodia, dynamic membrane protrusions driven by polymerization of an actin filament core, can adhere to the extracellular matrix and experience both external and cell-generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we study filopodia induced by overexpression of myosin X, typical for cancer cells. The lifetime of such filopodia positively correlates with the presence of myosin IIA filaments at the filopodia bases. Application of pulling forces to the filopodia tips through attached fibronectin-coated laser-trapped beads results in sustained growth of the filopodia. Pharmacological inhibition or knockdown of myosin IIA abolishes the filopodia adhesion to the beads. Formin inhibitor SMIFH2, which causes detachment of actin filaments from formin molecules, produces similar effect. Thus, centripetal force generated by myosin IIA filaments at the base of filopodium and transmitted to the tip through actin core in a formin-dependent fashion is required for filopodia adhesion.

Date: 2019
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DOI: 10.1038/s41467-019-10964-w

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