vinculinrelated

Vinculin-related refers to proteins that belong to the vinculin family and participate in cell–substrate and cell–cell adhesions. Vinculin itself is a cytoskeletal adaptor that coordinates the linkage between adhesion receptors and the actin cytoskeleton, enabling force transmission and mechanosensing at contact sites.

Structure and mechanism: Vinculin proteins commonly feature an N-terminal head domain that binds partners such as talin and alpha-actinin, a flexible central region, and a C-terminal tail that binds filamentous actin. In the resting state, intramolecular interactions keep binding sites hidden (autoinhibition); mechanical forces can unfold the molecule to reveal interaction surfaces, facilitating dynamic adhesion remodeling during cell migration and shape changes.

Members and isoforms: The best-characterized vertebrate members are vinculin and metavinculin. Metavinculin is a muscle-specific splice variant of the VCL gene with an insertion in the hinge region, which influences its binding properties and localization in muscle tissues, particularly at sites of strong contractile activity. In addition to these, other species contain vinculin homologs that participate in similar adhesion processes, illustrating the evolutionary conservation of this protein family.

Functions and localization: Vinculin-related proteins function at focal adhesions and adherens junctions, coordinating the assembly and disassembly of adhesion complexes, organizing actin networks, and transmitting mechanical signals between the extracellular matrix or neighboring cells and the cytoskeleton. They act as modular scaffolds that integrate signals from multiple binding partners to regulate cell adhesion, migration, and tissue mechanics.

Clinical relevance: Alterations in vinculin expression or function are implicated in diseases such as cardiomyopathy and certain myopathies, reflecting the importance of proper adhesion and force transmission in heart and muscle tissues. Abnormal vinculin signaling or localization can also affect cellular motility and cancer progression in some contexts. See also vinculin, metavinculin, focal adhesion.