Vinculin

Vinculin is a cytoskeletal protein that coordinates cell–matrix and cell–cell adhesions by linking integrins to the actin cytoskeleton. In humans it is encoded by the VCL gene. Vinculin localizes to focal adhesions and adherens junctions, where it acts as a scaffold that stabilizes connections between the plasma membrane and actin filaments. A muscle-specific splice variant called metavinculin is expressed in smooth and cardiac muscle and contributes to the integrity of muscle cell–cell junctions.

Structure and regulation: Vinculin contains an N-terminal head domain and a C-terminal tail domain that interact intramolecularly to maintain an autoinhibited state. Binding to talin, actin, and other partners, as well as lipid interactions with phosphatidylinositol 4,5-bisphosphate (PIP2), relieve autoinhibition and promote recruitment to adhesion sites. Mechanical tension across adhesions can also activate vinculin by extending the molecule to expose binding sites for additional actin- and adhesion-related proteins.

Functions: By coupling integrins to the actin cytoskeleton, vinculin stabilizes focal adhesions, regulates cell spreading and migration, and participates in mechanotransduction signaling that informs cells about substrate stiffness and geometry.

Interactions: Key partners include talin, actin, α‑actinin, paxillin, and other cytoskeletal adapters; vinculin can also interact with phospholipids such as PIP2.

Clinical relevance: Variants in VCL have been associated with inherited cardiomyopathies, including dilated cardiomyopathy, and with arrhythmias in some families. Research continues to clarify how vinculin dysfunction affects myocardial mechanics and cancer cell invasion.