Actin-dependent recruitment of Ago2 to the zonula adherens

Abstract

AbstractAdherens junctions are cadherin-based structures critical for cellular architecture. E-cadherin junctions in mature epithelial cell monolayers tether to an apical actomyosin ring to form the zonula adherens (ZA). We have previously shown that the adherens junction protein PLEKHA7 associates with and regulates the function of the core RNA interference (RNAi) component Ago2, specifically at the ZA. However, the mechanism mediating Ago2 recruitment to the ZA remained unexplored. Here, we reveal that this ZA-specific recruitment of Ago2 depends on both the structural and tensile integrity of the actomyosin cytoskeleton. We found that depletion of not only PLEKHA7, but also either of three PLEKHA7-interacting, LIM-domain family proteins, namely LMO7, LIMCH1, and PDLIM1, results in disruption of actomyosin organization and tension, as well as loss of Ago2 junctional localization. These results demonstrate that recruitment of Ago2 to the ZA is sensitive to actomyosin perturbations, introducing the idea of a mechanosensitive RNAi machinery, with potential implications in tissue remodeling and in disease.SummaryE-cadherin junctions at the zonula adherens recruit the key RNAi component Ago2 through a still unexplored mechanism. The present work shows that junctional recruitment of Ago2 depends on the integrity and tension of the actin cytoskeleton, revealing a mechanosensitive aspect of RNAi.