Interaction of the vinculin proline-rich linker region with vinexin α in sensing extracellular matrix stiffness

Abstract

Although extracellular matrix (ECM) stiffness is an important factor of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL region-binding protein vinexin are involved in sensing stiffness of ECM substrates. A rigid substrate increases cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these regulations. Furthermore, vinexin depletion impaired the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin α plays a critical role in sensing ECM stiffness and mechanotransduction.