Regulatory roles of microtubule-associated proteins in neuronal morphogenesis. Involvement of the extracellular matrix

As a result of recent investigations, the cytoskeleton can be viewed as a c ytoplasmic system of interconnected filaments with three major integrative levels: self-assembling macromolecules, filamentous polymers, e.g., microtu bules, intermediate filaments and actin filaments, and supramolecular struc tures formed by bundles of these filaments or networks resulting from cross -bridges between these major cytoskeletal polymers. The organization of thi s biological structure appears to be sensitive to fine spatially and tempor ally dependent regulatory signals. In differentiating neurons, regulation o f cytoskeleton organization is particularly relevant, and the microtubule-a ssociated protein (MAP) tau appears to play roles in the extension of large neuritic processes and axons as well as in the stabilization of microtubul ar polymers along these processes. Within this context, tau is directly inv olved in defining neuronal polarity as well as in the generation of neurona l growth cones. There is increasing evidence that elements of the extracell ular matrix contribute to the control of cytoskeleton organization in diffe rentiating neurons, and that these regulations could be mediated by changes in MAP activity. In this brief review, we discuss the possible roles of ta u in mediating the effects of extracellular matrix components on the intern al cytoskeletal arrays and its organization in growing neurons.