Figure 4. A model of switchable formation of adhesion sites via pre-assembled multi-protein building blocks.
The integrin adhesome is pre-assembled in the cytosol as multi-protein building blocks for adhesion sites. These building blocks are combinatorially diversified but confined in their size. Most of the building blocks form modules that are consistent with the previously reported (Kanchanawong et al., 2010) vertical continuum of anchoring, mechanosensing, and actin regulation layers across focal adhesions. In the cytosol, the pre-assembled building blocks cannot further assemble to form bigger structures due to mutual exclusiveness between protein interactions and allosteric regulations. On the plasma membrane, the system can get locally switched on to assemble an adhesion site by passing through checkpoints that enable additional protein interactions in the integrin adhesome. These checkpoints include anchoring of integrins to the extracellular matrix, mechanical stretching of proteins like talin and CAS by actomyosin contractility, and activation of proteins like vinculin and talin by PIP2 on the plasma membrane. Symmetric material exchange between adhesion sites and cytosol retains the wiring of the building blocks and therefore retains the assembly logic and switchability of the system.