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

Autor:	Wood MN; Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL.; The Driskill Graduate Training Program in Life Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL., Ishiyama N; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada., Singaram I; Department of Chemistry, University of Illinois at Chicago, Chicago, IL., Chung CM; Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL., Flozak AS; Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL., Yemelyanov A; Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL.; Department of Chemistry of Life Processes, Northwestern University, Feinberg School of Medicine, Chicago, IL., Ikura M; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.; Division of Signaling Biology, Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada., Cho W; Department of Chemistry, University of Illinois at Chicago, Chicago, IL.; Department of Genetic Engineering, Kyung Hee University, Yongin, Republic of Korea., Gottardi CJ; Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL c-gottardi@northwestern.edu.; Department of Cellular and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2017 Nov 06; Vol. 216 (11), pp. 3767-3783. Date of Electronic Publication: 2017 Sep 05.
DOI:	10.1083/jcb.201612006
Abstrakt:	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 KKR<3A mutant. Cells restored with a full-length, natively homodimerizing form of α-catenin KKR<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. (© 2017 Wood et al.)
Databáze:	MEDLINE
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