MOLECULAR-INTERACTIONS IN THE SUBMEMBRANE PLAQUE OF CELL-CELL AND CELL-MATRIX ADHESIONS

Adhesion of cells to their neighbors or to the extracellular matrix ha s multiple effects on cell shape, dynamics and fate. The most obvious and direct one is the assembly of single cells into ordered multicellu lar tissues and organs. This process requires specific transmembrane a dhesion molecules which mediate the binding to the external surface, c ytoskeletal filaments which attach to the cytoplasmic faces of the adh esion 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 ad dition, adhesive interactions have prominent, global consequences on c ell behavior and fate, affecting such processes as differentiation, gr owth and survival. To gain insight into the molecular basis for both t he local and global effects of adhesive interactions, we have chosen t o focus on one specific junctional domain, the submembrane plaque of m icrofilament-bound adhesions, namely cell-cell and cell-matrix adheren s junctions. Based on both biochemical and morphological evidence we w ould like to propose that the junctional plaque plays a key role in me diating and regulating transmembrane junctional interactions and adhes ion-dependent signaling. It offers multiple modes of linkage between t he cytoskeleton and the membrane, and its assembly can be controlled a t either the biosynthetic or posttranslational. levels. Furthermore, r ecent data demonstrate that the submembrane plaque is involved in the transduction of transmembrane signals. We will show that this structur e is the residence of an array of signaling enzymes (mostly kinases), that its structure and composition may be affected by activation of va rious signaling systems, and that adhesion itself may activate specifi c signal transduction pathways.