Regulation of Traction Force through the Direct Binding of Basigin and Calpain 4

Traction force and mechanosensing (the ability to sense the mechanical attributes of the environment) are two key factors that enable a cell to modify its behavior during migration. Previously, it was determined that the calpain small subunit, calpain 4 (CapnS1), regulates the production of traction force independent of its proteolytic holoenzyme. A proteolytic enzyme is formed by calpain 4 binding to either of its catalytic partners, calpain 1 and 2. To further understand how calpain 4 regulates traction force, we used two-hybrid analysis to identify more components of the traction pathway. We discovered that basigin, an integral membrane protein and a documented inducer of matrix-metalloprotease (MMP), binds to calpain 4 in two-hybrid and pull-down assays. Traction force was deficient when basigin was silenced in MEF cells, and this deficiency was also reflected in the defect in substrate adhesion strength. Unlike Capn4-/- MEF cells, the cells deficient in basigin had normal mechanosensing abilities. Together, these results implicate basigin in the pathway in which calpain 4 regulates traction force independent of the catalytic large subunits.