Inhibition of a negative feedback for persistent epithelial cell-cell junction contraction by p21-activated kinase 3

Abstract

Actin-mediated mechanical forces are central drivers of cellular dynamics. They generate protrusive and contractile dynamics, the latter of which are induced in concert with myosin II bundled at the site of contraction. These dynamics emerge concomitantly in tissues and even each cell; thus, the tight regulation of such bidirectional forces is important for proper cellular deformation. Here, we show that contractile dynamics can eventually disturb cell-cell junction contraction in the absence of p21-activated kinase 3 (Pak3). Upon Pak3 depletion, contractility induces the formation of abnormal actin protrusions at the shortening junctions, which reduces E-cadherin levels at adherens junctions. Such E-cadherin dilution dissociates myosin II from the contracting junctions, leading to a reduction in junctional tensile forces. Overexpressing E-cadherin restores the association of myosin II at the junctions and junction contraction. Our results suggest that contractility both induces and perturbs junction contraction and that the attenuation of such perturbations by Pak3 facilitates persistent junction shortening.