Figure 7.

Cell adhesion. Focal adhesions are complexes through which signals are transmitted to extracellular matrix (ECM) and interacting cells. Connection between focal adhesions and ECM is realized through subcellular structures, including integrins that bind to extracellular proteins. The intracellular domain of integrin binds to the cytoskeleton via adapter proteins. Other intracellular proteins associate with this complex. Adherens junctions are subapical structures that function as mediators of cell–cell adhesion. They have a crucial role as sensors of extracellular stimuli. Cadherins are principally responsible for cell–cell adhesion. The extracellular domain of cadherin forms complexes with the extracellular domains of cadherin on neighboring cells. The cytoplasmic domain of cadherin associates with catenins, which provide anchorage to the actin cytoskeleton. Tight junctions are areas of two cells forming an impermeable barrier. They are composed of sealing strands, each of which is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. Although different proteins are present, the major are claudins and occludins. These associate with different membrane proteins that anchor the strands to the actin cytoskeleton. Gap junctions are transmembrane channels that connect the cytoplasm of two cells, allowing various molecules to directly pass. Each single channel comprises two hemichannels composed by connexin proteins. The cytoplasmic domain of connexins binds to ZO-1, allowing the association between the gap and tight junctions. Desmosomes are structures specialized for cell-to-cell adhesion, arranged on the sides of plasma membrane and linking surface proteins to intracellular keratin filaments. The inner dense plaque proteins are attached to intermediate filaments. Pathway objects and links are described separately in Supplementary Figure 16.