The apical junction of epithelial cells can generate force to control cell geometry and perform contractile processes while maintaining barrier function and adhesion. Yet, the structural basis for force generation at the apical junction is not fully understood. Here, we describe two synaptopodin-dependent actomyosin structures that are spatially, temporally, and structurally distinct. The first structure is formed by the retrograde flow of synaptopodin initiated at the apical junction, creating a sarcomeric stress fiber that lies parallel to the apical junction. Contraction of the apical stress fiber is associated with either clustering of membrane components or shortening of junctional length. Upon junction maturation, apical stress fibers are disassembled. In mature epithelial monolayer, a motorized “contractomere” capable of “walking the junction” is formed at the junctional vertex. Actomyosin activities at the contractomere produce a compressive force evident by actin filament buckling and measurement with a new α-actinin-4 force sensor. The motility of contractomeres can adjust junctional length and change cell packing geometry during cell extrusion and intercellular movement. We propose a model of epithelial homeostasis that utilizes contractomere motility to support junction rearrangement while preserving the permeability barrier.
The apical junction of epithelial cells can generate force to control cell geometry and perform contractile processes while maintaining barrier function and cell-cell adhesion. Yet, the structural basis of force generation at the apical junction is not completely understood. Here, we describe 2 actomyosin structures at the apical junction containing synaptopodin, myosin IIB, and alpha-actinin-4. We showed that synaptopodin is required for the assembly of E-cadherin-associated apical stress fibers and a novel macromolecular structure, which we named contractomere. Knockdown of synaptopodin abolished both apical stress fiber and contractomere formation. Moreover, depletion of synaptopodin abolished basal stress fibers, converting myosin IIA sarcomere-like arrangement into a meshwork-type actomyosin organization. We propose a new model of junction dynamics that is dependent on contractomere movement to control epithelial cell boundary and geometry. Our findings reveal 2 actomyosin structures at the epithelial junction and underscore synaptopodin in the assembly of stress fibers and contractomeres.Summary StatementSynaptopodin assembles 2 actomyosin structures at the epithelial junction: apical stress fiber and contractomere. Synaptopodin selectively regulates myosin IIB without altering the level of myosin IIA and is responsible for converting evolutionary-conserved actomyosin meshwork into vertebrate-specific stress fibers.Graphic Abstract
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