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

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 e...

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Bibliographic Details
Published in:The Journal of cell biology 2017-11, Vol.216 (11), p.3767-3783
Main Authors: Wood, Megan N, Ishiyama, Noboru, Singaram, Indira, Chung, Connie M, Flozak, Annette S, Yemelyanov, Alex, Ikura, Mitsu, Cho, Wonhwa, Gottardi, Cara J
Format: Article
Language:English
Subjects:
alpha Catenin - genetics
alpha Catenin - metabolism
Animals
Cell Adhesion
Cell Line, Tumor
Cell Membrane - metabolism
Cell Movement
Dogs
Epithelial Cells - metabolism
Humans
Madin Darby Canine Kidney Cells
Mutation
Phosphatidylinositol 3-Kinase - metabolism
Phosphatidylinositol Phosphates - metabolism
Protein Binding
Protein Interaction Domains and Motifs
Protein Multimerization
Pseudopodia - metabolism
Signal Transduction
Time Factors
Transfection
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Summary: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-catenin mutant. Cells restored with a full-length, natively homodimerizing form of α-catenin 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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201612006