Laminin and the mechanism of neuronal outgrowth.

This review summarizes the structure of the laminin molecule and the role it plays in development, pathfinding and regeneration in the vertebrate nervous system. Laminin has proven to be an influential glycoprotein of the extracellular matrix which guides and promotes the differentiation and growth of neurons. Its numerous domains, its association with carbohydrate moieties, and its many isoforms associated with specific sites and stages will be important in elucidating its function. How laminin's signals become translated into changes in the behavior of cells remains one of the thorniest issues facing scientists working at the interface between neuronal growth cone and extracellular matrix. New approaches using molecular biological tools and immunological tools for dissecting the laminin molecule have provided hints of intramolecular shifts in laminin's properties which influence cell behavior. These shifts occur in response to other molecules in the extracellular matrix such as carbohydrates, or in response to moieties on the cell surface itself. Thus, reduction of laminin's structure to fragments and ultimately polypeptide sequences is leading to renewed significance of laminin's tertiary and quaternary structure with respect to laminin's biological interactions. Such insights about laminin's structure are providing new tools for probing growth cone behavior, tools that need to be coupled with equally sophisticated analyses of growth cone behavior using biophysical and biochemical measures at a biological level suitable for analyzing responses induced by the probes.