α-Catenin homodimers are recruited to phosphoinositide-activated membranes to promote adhesion

Megan N. Wood, Noboru Ishiyama, Indira Singaram, Connie M. Chung, Annette S. Flozak, Alex Yemelyanov, Mitsu Ikura, Wonhwa Cho, Cara Gottardi*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

A unique feature of α-catenin localized outside the cadherin-catenin complex is its capacity to form homodimers, but the subcellular localization and functions of this form of α-catenin remain incompletely understood. We identified a cadherin-free form of α-catenin that is recruited to the leading edge of migrating cells in a phosphatidylinositol 3-kinase- dependent manner. Surface plasmon resonance analysis shows that α-catenin homodimers, but not monomers, selectively bind phosphatidylinositol-3,4,5-trisphosphate-containing lipid vesicles with high affinity, where three basic residues, K488, K493, and R496, contribute to binding. Chemical-induced dimerization of α-catenin containing a synthetic dimerization domain promotes its accumulation within lamellipodia and elaboration of protrusions with extended filopodia, which are attenuated in the α-cateninKKR < 3A mutant. Cells restored with a full-length, natively homodimerizing form of α-cateninKKR < 3A display reduced membrane recruitment, altered epithelial sheet migrations, and weaker cell-cell adhesion compared with WT α-catenin. These findings show that α-catenin homodimers are recruited to phosphoinositide-activated membranes to promote adhesion and migration, suggesting that phosphoinositide binding may be a defining feature of α-catenin function outside the cadherin-catenin complex.

Original languageEnglish (US)
Pages (from-to)3767-3783
Number of pages17
JournalJournal of Cell Biology
Volume216
Issue number11
DOIs
StatePublished - Nov 1 2017

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ASJC Scopus subject areas

  • Cell Biology

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