An RPTPα/Src family kinase/Rap1 signaling module recruits myosin IIB to support contractile tension at apical E-cadherin junctions

Abstract

The role of myosin IIB in junctional contractility and its mode of regulation are not well understood. It is demonstrated that junctional recruitment of myosin IIB requires the activation of a receptor-type protein tyrosine phosphatase alpha–Src family kinase–Rap1 pathway. This reinforces the concept that E-cadherin–based signaling recruits distinct myosin II paralogues to generate contractile tension.

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

“…20 We then examined the localization of non-muscle myosin II in MCF-7 cells depleted of Coronin 1B, as E-cadherin and F-actin have been shown to influence the recruitment of non-muscle myosin II to junctions. 4,6,19 As previously described, 4,6,19 NMIIA and NMIIB concentrated prominently at the zonulae adherente of control MCF-7 monolayers (Fig. 1D, E).…”

“…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.…”

Adherens Junctions Revisualized: Organizing Cadherins as Nanoassemblies

“…Indeed, cadherins can promote actin assembly by coordinating cortical signaling and regulators of actin assembly to generate protrusive force (Cai et al, 2014). Third, the junctional actin cytoskeleton combined with cadherin signaling also recruits and activates myosin II (Gomez et al, 2015;Shewan et al, 2005;Smutny et al, 2010;Verma et al, 2012). This can generate contractile tension at junctions and influence junctional actin organization Wu et al, 2014).…”

Techniques to stimulate and interrogate cell–cell adhesion mechanics

“…Tension within cell–cell junctions can then be compared across experimental conditions by comparing initial recoil velocities. This approach has been used to determine the contributions of Src kinase [184], actin regulating proteins like N-WASP [185] and the Rho guanosine nucleotide exchange factor Ect2 [186], and myosin II [187] to the generation of tension at sites of cell–cell contact. Finally, this method is capable of measuring cell–cell forces both in traditional cell culture models as well as in vivo models like zebrafish [188].…”