Geiger B, Yehuda-Levenberg S, Bershadsky A D
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Acta Anat (Basel). 1995;154(1):46-62. doi: 10.1159/000147751.
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.
细胞与其相邻细胞或细胞外基质的黏附对细胞形态、动力学和命运具有多种影响。最明显和直接的影响是将单细胞组装成有序的多细胞组织和器官。这个过程需要特定的跨膜黏附分子，其介导与外表面的结合；细胞骨架细丝，其附着于黏附位点的细胞质面；以及一个将两者相互连接的膜下斑块。这些连接结构域的共同组装对于形成具有适当机械性能的稳定细胞黏附至关重要。此外，黏附相互作用对细胞行为和命运具有显著的全局影响，影响诸如分化、生长和存活等过程。为了深入了解黏附相互作用的局部和全局影响的分子基础，我们选择专注于一个特定的连接结构域，即微丝结合黏附的膜下斑块，也就是细胞间和细胞与基质的黏着连接。基于生化和形态学证据，我们提出连接斑块在介导和调节跨膜连接相互作用及黏附依赖性信号传导中起关键作用。它提供了细胞骨架与膜之间的多种连接方式，其组装可以在生物合成或翻译后水平受到控制。此外，最近的数据表明膜下斑块参与跨膜信号的转导。我们将表明这种结构是一系列信号酶（主要是激酶）的驻留位点，其结构和组成可能受到各种信号系统激活的影响，并且黏附本身可能激活特定的信号转导途径。
