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

Christopher P Toret1, Michael V D'Ambrosio, Ronald D Vale

  • 1Department of Biology and 2 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.

The Journal of Cell Biology
|January 22, 2014
PubMed

Insights

Researchers identified key proteins regulating cell adhesion by conducting a large-scale RNA interference screen in Drosophila. This study uncovers new pathways essential for cadherin-mediated cell-cell adhesion across Metazoa.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genomics

Background:

  • Cadherins and catenins are crucial for cell-cell adhesion and link to the actin cytoskeleton and signaling pathways.
  • The complete set of proteins and pathways involved in cadherin-mediated adhesion remains incompletely understood.

Purpose of the Study:

  • To identify novel proteins and pathways regulating cadherin-mediated cell-cell adhesion.
  • To establish a comprehensive inventory of factors involved in this fundamental biological process.

Main Methods:

  • Genome-wide RNA interference (RNAi) screen targeting Ca(2+)-dependent adhesion in Drosophila S2 cells.
  • Analysis of protein-protein interactions and functional networks.
  • Validation in Drosophila oogenesis and mammalian Madin-Darby canine kidney cells.

Main Results:

  • A genome-wide screen identified 17 interconnected regulatory hubs controlling cadherin-catenin complex levels and adhesion.
  • The screen specifically focused on Ca(2+)-dependent adhesion, excluding other cellular processes.
  • Further analysis confirmed roles for diverse pathways, including cytoskeleton organization and signaling.

Conclusions:

  • Cadherin-mediated adhesion is regulated by a complex network of proteins and pathways.
  • This study provides a foundational understanding of the molecular machinery governing cell-cell adhesion in Metazoa.
  • Identified pathways are conserved and essential for cadherin function across different species.

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