2. Academic Validation
  3. α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism

α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism

  • J Cell Sci. 2015 Mar 15;128(6):1150-65. doi: 10.1242/jcs.163824.
David J Escobar 1,  Ridhdhi Desai 2,  Noboru Ishiyama 3,  Stephen S Folmsbee 1,  Megan N Novak 1,  Annette S Flozak 4,  Rebecca L Daugherty 1,  Rigen Mo 4,  Dhaval Nanavati 5,  Ritu Sarpal 2,  Deborah Leckband 6,  Mitsu Ikura 3,  Ulrich Tepass 7,  Cara J Gottardi 8
Affiliations

Affiliations

  • 1 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA The Driskill Graduate Training Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 2 Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5 Canada.
  • 3 University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, ON M5T 2M9, Canada.
  • 4 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 5 Department of Chemistry of Life Processes, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 6 Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, IL 61801, USA.
  • 7 Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5 Canada [email protected] [email protected].
  • 8 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Department of Cellular and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA [email protected] [email protected].
PMID: 25653389 DOI: 10.1242/jcs.163824
Abstract

The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian αE-catenin (also known as catenin α-1) and Drosophila α-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of α-catenin in cells and is sequentially modified at Casein Kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal α-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of α-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of α-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the α-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

Keywords

Adhesion; Migration; Phospho-regulation; α-catenin.

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