title: α-Catenin uses a novel mechanism to activate vinculin.
abstract: Vinculin, an actin-binding protein, is emerging as an important regulator of adherens junctions. In focal-adhesions, vinculin is activated by simultaneous binding of talin to its head domain and actin filaments to its tail domain. Talin is not present in adherens junctions. Consequently, the identity of the ligand that activates vinculin in cell-cell junctions is not known. Here we show that in the presence of F-actin, α-catenin, a cytoplasmic component of the cadherin adhesion complex, activates vinculin. Direct binding of α-catenin to vinculin is critical for this event because a point mutant (α-catenin L344P) lacking high affinity binding does not activate vinculin. Furthermore, unlike all known vinculin activators, α-catenin binds to and activates vinculin independently of an A50I substitution in the vinculin head, a mutation that inhibits vinculin binding to talin and IpaA. Collectively, these data suggest that α-catenin employs a novel mechanism to activate vinculin and may explain how vinculin is differentially recruited and/or activated in cell-cell and cell-matrix adhesions.
authors.affiliation: Department of Biochemistry, University of Iowa Roy J. Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Maiers
authors.forename: Dilshad
authors.initials: D
authors.lastname: Choudhury
authors.forename: Susan W
authors.initials: SW
authors.lastname: Craig
authors.forename: Kris A
authors.initials: KA
authors.lastname: DeMali
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017354:Point Mutation; D011485:Protein Binding; D016596:Vinculin / Q000235:genetics / Q000378:metabolism*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C488955:VCL protein, human; D051178:alpha Catenin; D016596:Vinculin