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

David J. Escobar, Ridhdhi Desai, Noboru Ishiyama, Stephen S. Folmsbee, Megan N. Novak, Annette S. Flozak, Rebecca L. Daugherty, Rigen Mo, Dhaval Nanavati, Ritu Sarpal, Deborah Leckband, Mitsu Ikura, Ulrich Tepass*, Cara J. Gottardi

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

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, nonphosphorylatable forms of a-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of a-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the a-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

Original languageEnglish (US)
Pages (from-to)1150-1165
Number of pages16
JournalJournal of cell science
Volume128
Issue number6
DOIs
StatePublished - 2015

Keywords

  • Adhesion
  • Migration
  • Phospho-regulation
  • α-catenin

ASJC Scopus subject areas

  • Cell Biology

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    Escobar, D. J., Desai, R., Ishiyama, N., Folmsbee, S. S., Novak, M. N., Flozak, A. S., Daugherty, R. L., Mo, R., Nanavati, D., Sarpal, R., Leckband, D., Ikura, M., Tepass, U., & Gottardi, C. J. (2015). α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism. Journal of cell science, 128(6), 1150-1165. https://doi.org/10.1242/jcs.163824