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  • A genome-wide screen identifies conserved protein hubs required for cadherin-mediated cell-cell adhesion.

A genome-wide screen identifies conserved protein hubs required for cadherin-mediated cell-cell adhesion.

The Journal of cell biology (2014-01-22)
Christopher P Toret, Michael V D'Ambrosio, Ronald D Vale, Michael A Simon, W James Nelson
ABSTRACT

Cadherins and associated catenins provide an important structural interface between neighboring cells, the actin cytoskeleton, and intracellular signaling pathways in a variety of cell types throughout the Metazoa. However, the full inventory of the proteins and pathways required for cadherin-mediated adhesion has not been established. To this end, we completed a genome-wide (~14,000 genes) ribonucleic acid interference (RNAi) screen that targeted Ca(2+)-dependent adhesion in DE-cadherin-expressing Drosophila melanogaster S2 cells in suspension culture. This novel screen eliminated Ca(2+)-independent cell-cell adhesion, integrin-based adhesion, cell spreading, and cell migration. We identified 17 interconnected regulatory hubs, based on protein functions and protein-protein interactions that regulate the levels of the core cadherin-catenin complex and coordinate cadherin-mediated cell-cell adhesion. Representative proteins from these hubs were analyzed further in Drosophila oogenesis, using targeted germline RNAi, and adhesion was analyzed in Madin-Darby canine kidney mammalian epithelial cell-cell adhesion. These experiments reveal roles for a diversity of cellular pathways that are required for cadherin function in Metazoa, including cytoskeleton organization, cell-substrate interactions, and nuclear and cytoplasmic signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-l-Afadin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Cytoplasmic FMR1-interacting protein 1 Antibody, from rabbit, purified by affinity chromatography