TY - JOUR
T1 - α-Catenin uses a novel mechanism to activate vinculin
AU - Peng, Xiao
AU - Maiers, Jessica L.
AU - Choudhury, Dilshad
AU - Craig, Susan W.
AU - DeMali, Kris A.
PY - 2012/3/2
Y1 - 2012/3/2
N2 - 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 cellcell and cell-matrix adhesions.
AB - 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 cellcell and cell-matrix adhesions.
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U2 - 10.1074/jbc.M111.297481
DO - 10.1074/jbc.M111.297481
M3 - Article
C2 - 22235119
AN - SCOPUS:84857726052
SN - 0021-9258
VL - 287
SP - 7728
EP - 7737
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 10
ER -