Functional organization of tau proteins during neuronal differentiation and development.
Tau proteins play major regulatory roles in the organization and integrity of the cytoskeletal network. In neurons, a specific axonal compartmentalization of tau has been shown. However, recent studies demonstrate that tau displays a widespread distribution in a variety of non-neuronal cell types. These proteins have been found in human fibroblasts and in several transformed cell lines. The heterogeneous family of tau is formed by a set of molecular species that share common peptide sequences. There is a single gene that contains several exons encoding for the six different tau isoforms in mammalian brain. Alternative splicing of a common RNA transcript as well as post-translational modifications contribute to its heterogeneity. Tau isoforms generated by splicing differ from one another by having either three or four repeats in their C-terminal half, and a variable number of inserts in their N-terminal moiety. These repeats have been shown to constitute microtubule-binding motifs. In this review some relevant aspects of tau function and its regulation are analyzed. Three major topics are discussed. The first one focuses on the tau roles in regulating the interactions between microtubules with actin filaments and with intermediate filament systems. Another problem deals with the question of whether tau isoforms segregate into functionally different subsets of microtubules in axonal processes, or tau associates with these polymers in a random fashion. The third question that emerges is the involvement of tau and tau-like proteins in morphogenetic events. The regulation of the interactions of DMAP-85, a recently discovered tau-like protein, with the cytoskeleton during development of Drosophila melanogaster is analyzed.
Maccioni
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RB
Laboratory of Cellular and Molecular Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Tapia
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Cambiazo
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D004331:Drosophila melanogaster / Q000254:growth & development; D008868:Microtubule Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D016875:tau Proteins / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D008868:Microtubule Proteins; D016875:tau Proteins