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. Epub 2015 Feb 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Casein Kinase I / genetics
  • Casein Kinase I / metabolism*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Cell Adhesion*
  • Cell Membrane / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dogs
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoprecipitation
  • Madin Darby Canine Kidney Cells
  • Molecular Sequence Data
  • Ovary / cytology
  • Ovary / metabolism
  • Phosphorylation
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • alpha Catenin / chemistry
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*

Substances

  • Actins
  • Cadherins
  • alpha Catenin
  • Casein Kinase I
  • Casein Kinase II