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; A. D. Bershadsky

doi:10.1038/s41467-019-10964-w

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, A. D. Bershadsky

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Article number	3593
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10964-w
State	Published - Dec 1 2019
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-019-10964-w

Cite this

@article{a8abab6bf21b439b9a70c74dc46b5eca,

title = "Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion",

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.",

author = "Alieva, {N. O.} and Efremov, {A. K.} and S. Hu and D. Oh and Z. Chen and M. Natarajan and Ong, {H. T.} and A. J{\'e}gou and G. Romet-Lemonne and Groves, {J. T.} and Sheetz, {M. P.} and J. Yan and Bershadsky, {A. D.}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-10964-w",

language = "English (US)",

volume = "10",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion

AU - Alieva, N. O.

AU - Efremov, A. K.

AU - Hu, S.

AU - Oh, D.

AU - Chen, Z.

AU - Natarajan, M.

AU - Ong, H. T.

AU - Jégou, A.

AU - Romet-Lemonne, G.

AU - Groves, J. T.

AU - Sheetz, M. P.

AU - Yan, J.

AU - Bershadsky, A. D.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85070634508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070634508&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10964-w

DO - 10.1038/s41467-019-10964-w

M3 - Article

C2 - 31399564

AN - SCOPUS:85070634508

SN - 2041-1723

VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3593

ER -

Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this