Generation of stress fibers through myosin-driven re-organization of the actin cortex

Abstract

<jats:title>Summary</jats:title><jats:p>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 <jats:italic>de novo</jats:italic> from the actin cortex, and establish role for stochastic myosin pulses in the assembly of functional actomyosin bundles.</jats:p>

Cellular functions of actin- and microtubule-associated septins

“…SEPT9_i2 inhibits cell migration and the formation of a subset of actin stress fibers that localize on the ventral side of the nucleus 38 . New work shows that these stress fibers assemble through re-organization of the cortical actin by myosin II, which might be regulated by SEPT9 isoforms 91 . SEPT9_i3 has also been found to interact with and inhibit a septin-associated Rho guanine nucleotide exchange factor (SA-RhoGEF) 59 .…”

DAAM mediates the assembly of long-lived, treadmilling stress fibers in collectively migrating epithelial cells in Drosophila

“…First, DAAM is found throughout the cortex with no obvious enrichment at adhesions. Second, treadmilling SFs closely resemble other SF types that arise from the cortex and/or are embedded within it (Lehtimäki et al, 2021; Svitkina, 2020; Vignaud et al, 2020), as they lie so flat against the basal surface that we can visualize them with near-TIRF microscopy. This contrasts with ventral SFs whose center can arch away from the migratory surface.…”

“…To our knowledge this is the first study to focus on the role of internal adhesions in SF dynamics, but there are hints in the literature that these structures may exist in other cells. For example, SFs isolated from human foreskin fibroblasts and bovine endothelial cells have small puncta of the focal adhesion protein vinculin along their lengths in addition to prominent vinculin puncta at their ends (Katoh et al, 1998), and the cortical SFs in cultured mesenchymal cells were sometimes observed to have more than two adhesions (Lehtimäki et al, 2021). Internal adhesions have also been invoked as a possible explanation for the buckling pattern observed when SFs are rapidly compressed (Costa et al, 2002; Kassianidou and Kumar, 2015).…”

“…SFs are prominent F-actin bundles that have been categorized into different types based on their origin, subcellular location, and how they interact with non-muscle myosin II and integrin-based focal adhesions (Burridge and Guilluy, 2016; Burridge and Wittchen, 2013; Naumanen et al, 2008; Tojkander et al, 2012; Vallenius, 2013). The most studied SF types have myosin along their lengths and large focal adhesions at either end; these include ventral SFs (Hotulainen and Lappalainen, 2006; Tojkander et al, 2015) and the recently defined cortical SFs (Lehtimäki et al, 2021). SFs play key roles in focal adhesion maturation, defining the cell’s front-rear axis, retraction of the trailing edge, and sensing the mechanical properties of the ECM (Lehtimäki et al, 2017; Livne and Geiger, 2016; Schwartz, 2010).…”

Intra-bundle contractions enable extensile properties of active actin networks

“…Although previous work has demonstrated high dynamics 11,13 or strong contractility 14 in reconstituted active actomyosin cortices, the system presented here establishes an important bridge between the two extremes. Ultimately, these findings can explain the molecular basis of how active actin cortices break symmetry to initiate polarized cell motility 45 or even generate stress fibers 46 within highly dynamic lamellipodia by means of NMMII mediated actin reorganization.…”