Cortical F-actin stabilization generates apical–lateral patterns of junctional contractility that integrate cells into epithelia

Abstract

E-cadherin cell-cell junctions couple the contractile cortices of epithelial cells together, generating tension within junctions that influences tissue organization. Although junctional tension is commonly studied at the apical zonula adherens, we now report that E-cadherin adhesions induce the contractile actomyosin cortex throughout the apical-lateral axis of junctions. However, cells establish distinct regions of contractile activity even within individual contacts, producing high tension at the zonula adherens but substantially lower tension elsewhere. We demonstrate that N-WASP (also known as WASL) enhances apical junctional tension by stabilizing local F-actin networks, which otherwise undergo stress-induced turnover. Further, we find that cells are extruded from monolayers when this pattern of intra-junctional contractility is disturbed, either when N-WASP redistributes into lateral junctions in H-Ras(V12)-expressing cells or on mosaic redistribution of active N-WASP itself. We propose that local control of actin filament stability regulates the landscape of intra-junctional contractility to determine whether or not cells integrate into epithelial populations.

Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking

“…Our data add another layer to our understanding of the function of myosin II in exocytosis. By maintaining tension of the cortical actin network 18,19,40 in unstimulated cells, myosin II retains most SVs away from the plasma membrane. This is in good agreement with previous reports showing that the cortical actin network acts as a barrier, preventing the majority of vesicles from accessing the plasma membrane in resting conditions 2,9 .…”

“…To measure cortical tension, we used laser nanoablation 19 to cut the cortical actin network. We then measured the instantaneous rate of recoil as an index of cortical actin network tension 30 .…”

“…SVs can be tethered to the cortical actin network by myosin VI in an activity-dependent manner 10 , and can also be transported along actin fibres by myosin Va 11 . Recent work has also highlighted a role for myosin II in exocytosis [12][13][14][15][16][17] , as well as demonstrating its ability to maintain the cortical actin network under tension [18][19][20] . How these molecular motors act to direct SVs towards their docking sites remains unclear.…”

Coronin 1B supports RhoA signaling at cell-cell junctions through Myosin II

“…1,2 In epithelia, prominent contractile networks are found in the apical poles of embryonic epithelial cells (medioapical networks 3 ) and at the cortices of cell-cell adherens junctions (AJ). [4][5][6] At the AJs, actomyosin networks interact with E-cadherin-based adhesions that couple adjacent cells together to form cohesive monolayers. These structures are especially apparent in polarized epithelial cells, where prominent actomyosin bundles lie adjacent to the E-cadherin rings found at the apical region of cell-cell junctions, also known as the zonula adherens (ZA).…”

“…These structures are especially apparent in polarized epithelial cells, where prominent actomyosin bundles lie adjacent to the E-cadherin rings found at the apical region of cell-cell junctions, also known as the zonula adherens (ZA). [4][5][6] The physical coupling of actomyosin to E-cadherin adhesions results in contractile tension at junctions, which supports tissue cohesion, epithelial integrity and morphogenesis. [7][8][9][10][11][12][13] The assembly and activity of junctional actomyosin is subject to regulation by numerous cell signaling pathways.…”