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

作者：Wood Megan N; Ishiyama Noboru; Singaram Indira; Chung Connie M; Flozak Annette S; Yemelyanov Alex; Ikura Mitsu; Cho Wonhwa; Gottardi Cara J^*

来源：The Journal of Cell Biology, 2017, 216(11): 3767-3783.

DOI：10.1083/jcb.201612006

A unique feature of alpha-catenin localized outside the cadherin-catenin complex is its capacity to form homodimers, but the subcellular localization and functions of this form of alpha-catenin remain incompletely understood. We identified a cadherin-free form of alpha-catenin that is recruited to the leading edge of migrating cells in a phosphatidylinositol 3-kinase-dependent manner. Surface plasmon resonance analysis shows that alpha-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 alpha-catenin containing a synthetic dimerization domain promotes its accumulation within lamellipodia and elaboration of protrusions with extended filopodia, which are attenuated in the alpha-catenin(KKR<3A) mutant. Cells restored with a full-length, natively homodimerizing form of alpha-catenin(KKR<3A) display reduced membrane recruitment, altered epithelial sheet migrations, and weaker cell-cell adhesion compared with WT alpha-catenin. These findings show that alpha-catenin homodimers are recruited to phosphoinositide-activated membranes to promote adhesion and migration, suggesting that phosphoinositide binding may be a defining feature of alpha-catenin function outside the cadherin-catenin complex.

• 出版日期2017-11
• 单位西北大学