Generation of stress fibers through myosin-driven reorganization of the actin cortex.

Jaakko I Lehtimäki,Eeva Kaisa Rajakylä,Pekka Lappalainen,Sari Tojkander

doi:10.7554/elife.60710

Abstract

Contractile actomyosin bundles, stress fibers, govern key cellular processes including migration, adhesion, and mechanosensing. Stress fibers are thus critical for developmental morphogenesis. The most prominent actomyosin bundles, ventral stress fibers, are generated through coalescence of pre-existing stress fiber precursors. However, whether stress fibers can assemble through other mechanisms has remained elusive. We report that stress fibers can also form without requirement of pre-existing actomyosin bundles. These structures, which we named cortical stress fibers, are embedded in the cell cortex and assemble preferentially underneath the nucleus. In this process, non-muscle myosin II pulses orchestrate the reorganization of cortical actin meshwork into regular bundles, which promote reinforcement of nascent focal adhesions, and subsequent stabilization of the cortical stress fibers. These results identify a new mechanism by which stress fibers can be generated de novo from the actin cortex and establish role for stochastic myosin pulses in the assembly of functional actomyosin bundles.

Highlights

Cell migration, morphogenesis, and adhesion depend on contractile networks composed of actin and non-muscle myosin II (NMII) filaments
The actin cortex harbors cortical stress fibers of various size and orientation Ventral stress fibers were originally defined as contractile actomyosin bundles, which attach to focal adhesions at their both ends (Small et al, 1998; Hotulainen and Lappalainen, 2006)
Because dorsal stress fibers elongate through actin polymerization at focal adhesions (Hotulainen and Lappalainen, 2006; Tee et al, 2015; Tojkander et al, 2015), we examined the possible role of actin filament assembly at adhesions in the formation of cortical stress fibers

Summary

Introduction

Morphogenesis, and adhesion depend on contractile networks composed of actin and non-muscle myosin II (NMII) filaments. Dorsal stress fibers ( known as radial fibers) are non-contractile actin filament bundles that are generated at the cell front through formin- and VASP-mediated actin filament assembly at focal adhesions (Hotulainen and Lappalainen, 2006; Tee et al, 2015; Tojkander et al, 2015). We show that different cell types exhibit, at their ventral actin cortex, thin stress fibers that are connected to focal adhesions at both ends These actomyosin bundles form predominantly underneath the nucleus, and are less contractile and more dynamic compared to the ventral stress fibers, which are derived through fusion of transverse arcs at the lamella of migrating cells. They are generated de novo from the actin cortex through NMIIA-driven reorganization of the actin filament meshwork, and we call them as cortical stress fibers

Results

Discussion

Materials and methods