ABSTRACT
The importance of cell adhesion molecules as determinants of tissue architecture has long been recognized. These molecules mediate cell-cell and cell-substrate adhesion and thereby play critical roles in a variety of biological processes including development, tumorigenesis, and in ammation. Our understanding of cell-matrix and cell-cell adhesion has increased signi cantly in the last decade with the identi cation of the molecular components of adhesion complexes, as well as their structure and organization. Importantly, it has become apparent that adhesion molecules are not merely cellular “glue” but highly dynamic complexes that can play important roles in cell signaling. This chapter will highlight the growing volume of evidence showing that cell adhesion complexes may be important molecular targets for a variety of toxic metals such as manganese, cadmium, mercury, copper, lead, and arsenic. Speci c examples of metal-induced disruption of adhesion complexes will be included, as well as the latest information on molecular mechanisms by which metals may in uence cellular adhesion. While disruption of cell adhesion is a relatively new mechanistic
12.1 Introduction .......................................................................................................................... 327 12.2 Overview of Cell Adhesion Molecules ................................................................................. 328
12.2.1 Integrins: Cell-Matrix Interactions .......................................................................... 328 12.2.2 Homotypic Cell-Cell Adhesion ................................................................................ 330
12.2.2.1 Tight Junction............................................................................................. 330 12.2.2.2 Cadherin Complex ..................................................................................... 330 12.2.2.3 Gap Junctions ............................................................................................. 331
12.2.3 Heterotypic Cell-Cell Adhesion: In ammation ....................................................... 332 12.3 Metal-Induced Disruption of Cell Adhesion ........................................................................ 332
12.3.1 Integrins .................................................................................................................... 332 12.3.2 Tight Junctions and Cadherin/Catenin Complexes .................................................. 333 12.3.3 Gap Junctions ............................................................................................................ 334 12.3.4 In ammatory Adhesion Molecules .......................................................................... 335
12.4 Potential Mechanisms ........................................................................................................... 335 12.4.1 Gene Expression ....................................................................................................... 335 12.4.2 Protein-Protein Interactions ..................................................................................... 336 12.4.3 Protein Phosphorylation............................................................................................ 336 12.4.4 Protein Degradation .................................................................................................. 337 12.4.5 Disruption of the Actin Cytoskeleton ....................................................................... 338 12.4.6 Oxidative Stress ........................................................................................................ 338
12.5 Conclusions ........................................................................................................................... 338 References ...................................................................................................................................... 339
consideration in metal toxicology and fewer studies have been conducted in this area than in other topics discussed in this book, it is clear that the actions of metals on cell adhesion molecules must be evaluated when considering the impact of metal exposure on human health.
