CYTOSKELETON AND CELL-ADHESION MOLECULES - CRITICAL TARGETS OF TOXIC AGENTS

Normal development of the nervous system depends upon complex physical interactions between cells and their local environment. These interac tions are mediated by several families of cell adhesion molecules (CAM s). Differential expression and function of CAMs are operative in neur al tube formation, neuron migration, in post-migratory differentiation , and maintenance of mature neural structure. CAMs also facilitate con tact-dependent cell processes, such as formation of cell junctions. Te mporal regulation of these molecules during development may provide '' windows of vulnerability'' to toxicants. in addition to their extracel lular binding activities, some CAMs have membrane-spanning domains by which they communicate directly with the cytoskeleton, permitting extr a cellular signals to be rapidly translated into cell responses via mo difications in cytoskeletal organization. These cytologic changes are particularly critical during migration, neurite formation and synaptog enesis. Toxic perturbation of adhesion molecules can ha ve catastrophi c effects on morphogenetic processes both directly and via events whic h depend upon cytoskeletal rearrangement. Toxicants can also act direc tly upon the cytoskeleton, resulting secondarily in changes of the mem brane distribution and function of CAMs. Toxicant-induced changes in C AMs and cytoskeleton may occur contemporaneously. Interference of cell adhesion-cytoskeleton interactions may be a pivotal molecular event d ictating developmental consequences of neurotoxicant exposure. (C) 199 4 Intox Press, Inc.