Figure 1.

Integrated mechanotransduction of cadherins and integrins through the cytoskeleton and small GTPases. A. At cell–cell adhesion points coupled cadherins transduce strain and shear force into cytoskeletal remodeling and downstream signaling pathways. B. At cell–extracellular matrix (ECM) adhesions, strain is transduced through integrins into cytoskeletal remodeling and downstream signaling pathways. C. RhoA and Rac are mechano-sensitive small GTPases common to multiple methods of mechanotransduction in the mitral valve that act opposite and complementary to control cell migration, differentiation, and proliferation. RhoA regulates actin cytoskeleton and stress fiber formation while Rac1 regulates cell–cell adhesion, actin polymerization, lamellae protrustion, and cytoskeletal polarity. ROCK interacts with integrins and cadherins to mediate RhoA and Rac activity while FilGAP binds to filamin-A to control actin at cytoskeletal interfaces. D. The extracellular matrix interacts with the actin network directly through specific ECM components or through integrins and cadherins. See Section “Integrated Mechanotransduction” for more information.