Molecular interactions in the submembrane plaque of cell-cell and cell-matrix adhesions.

Adhesion of cells to their neighbors or to the extracellular matrix has multiple effects on cell shape, dynamics and fate. The most obvious and direct one is the assembly of single cells into ordered multicellular tissues and organs. This process requires specific transmembrane adhesion molecules which mediate the binding to the external surface, cytoskeletal filaments which attach to the cytoplasmic faces of the adhesion site, and a submembrane plaque which interconnects the two. The co-assembly of these junctional domains is essential for the formation of stable cell adhesions with the proper mechanical properties. In addition, adhesive interactions have prominent, global consequences on cell behavior and fate, affecting such processes as differentiation, growth and survival. To gain insight into the molecular basis for both the local and global effects of adhesive interactions, we have chosen to focus on one specific junctional domain, the submembrane plaque of microfilament-bound adhesions, namely cell-cell and cell-matrix adherens junctions. Based on both biochemical and morphological evidence we would like to propose that the junctional plaque plays a key role in mediating and regulating transmembrane junctional interactions and adhesion-dependent signaling. It offers multiple modes of linkage between the cytoskeleton and the membrane, and its assembly can be controlled at either the biosynthetic or posttranslational levels. Furthermore, recent data demonstrate that the submembrane plaque is involved in the transduction of transmembrane signals. We will show that this structure is the residence of an array of signaling enzymes (mostly kinases), that its structure and composition may be affected by activation of various signaling systems, and that adhesion itself may activate specific signal transduction pathways.