ULP-2 SUMO Protease Regulates E-Cadherin Recruitment to Adherens Junctions

• ULP-2 SUMO protease regulates epidermal morphogenesis
• The cadherin-catenin complex is a target for ULP-2 activity
• Sumoylation of HMR-1/E-cadherin cytoplasmic tail impairs HMP-2/β-catenin binding
• Reversible sumoylation of HMR-1 is needed for its recruitment to adherens junctions

SummaryAdherens junctions (AJs) are membrane-anchored structures composed of E-cadherin and associated proteins, including catenins and actin. The unique plasticity of AJs mediates both the rigidity and flexibility of cell-cell contacts essential for embryonic morphogenesis and adult tissue remodeling. We identified the SUMO protease ULP-2 as a regulator of AJ assembly and show that dysregulated ULP-2 activity impairs epidermal morphogenesis in Caenorhabditis elegans embryos. The conserved cytoplasmic tail of HMR-1/E-cadherin is sumoylated and is a target of ULP-2 desumoylation activity. Coupled sumoylation and desumoylation of HMR-1 are required for its recruitment to the subapical membrane during AJ assembly and the formation of the linkages between AJs and the apical actin cytoskeleton. Sumoylation weakens HMR-1 binding to HMP-2/β-catenin. Our study provides a mechanistic link between the dynamic nature of the SUMO machinery and AJ plasticity and highlight sumoylation as a molecular switch that modulates the binding of E-cadherin to the actin cytoskeleton.

Graphical AbstractFigure optionsDownload high-quality image (178 K)Download as PowerPoint slide