The Art of Vinculin Activation

Vinculin is a 117-kDa cytoskeletal protein which acts as a cross linker in cell to cell adhesions of the extracellular membrane. The protein has a globular head domain that contains binding sites for talin, α-actinin and a tyrosine phosphorylation site. The tail region contains binding sites for F-actin, paxillin, and regulatory lipids Integrins are coupled to the actin cytoskeleton by a series of actin-binding proteins including vinculin. Upon loss of its intramolecular head-tail interaction, vinculin transitions from its closed, inactive conformation to its open, active conformation. In its open conformation, vinculin binds many proteins, including talin and actin. Vinculin is able to control the cells motility by simply altering its shape from active to inactive, which is especially important in regulating the movement of cancer cells within the body. Here, actin is shown in red while vinculin in blue is in its inactive state, waiting to be bound and activated by talin in black. Throughout the dance every protein has its own unique style of movement. Talin activates and interacts with vinculin in a pas de deux while actin migrates toward the focal adhesion. Finally, all three proteins are complexed together inside of the focal adhesion, symbolized by the unification of their movements.