FUNCTIONAL-ORGANIZATION OF TAU-PROTEINS DURING NEURONAL DIFFERENTIATION AND DEVELOPMENT

Tau proteins play major regulatory roles in the organization and integ rity of the cytoskeletal network. In neurons, a specific axonal compar tmentalization of tau has been shown. However, recent studies demonstr ate that tau displays a widespread distribution in a variety of non-ne uronal cell types. These proteins have been found in human fibroblasts and in several transformed cell lines. The heterogenous family of tau is formed by a set of molecular species that share common peptide seq uences. There is a single gene that contains several exons encoding fo r the six different tau isoforms in mammalian brain. Alternative splic ing of a common RNA transcript as well as post-translational modificat ions contribute to its heterogeneity. Tau isoforms generated by splici ng differ from one another by having either three or four repeats in t heir C-terminal half, and a variable number of inserts in their N-term inal moiety. These repeats have been shown to constitute microtubule b inding motifs. In this review some relevant aspects of tau function an d its regulation are analyzed. Three major topics are discussed. The f irst one focuses on the tau roles in regulating the interactions betwe en microtubules with actin filaments and with intermediate filament sy stems. Another problem deals with the question of whether tau isoforms segregate into functionally different subsets of microtubules in axon al processes, or tau associates with these polymers in a random fashio n. The third question that emerges is the involvement of tau and tau-l ike proteins in morphogenetic events. The regulation of the interactio ns of DMAP-85, a recently discovered tau-like protein, with the cytosk eleton during development of Drosophila melanogaster is analyzed.