Self protein-protein interactions are involved in TPPP/p25 mediated microtubule bundling.

Abstract : TPPP/p25 is a microtubule-associated protein, detected in protein inclusions associated with various neurodegenerative diseases. Deletion analysis data show that TPPP/p25 has two microtubule binding sites, both located in intrinsically disordered domains, one at the N-terminal and the other in the C-terminal domain. In copolymerization assays the full-length protein exhibits microtubule stimulation and bundling activity. In contrast, at the same ratio relative to tubulin, truncated forms of TPPP/p25 exhibit either lower or no microtubule stimulation and no bundling activity, suggesting a cooperative phenomenon which is enhanced by the presence of the two binding sites. The binding characteristics of the N- and C-terminally truncated proteins to taxol-stabilized microtubules are similar to the full-length protein. However, the C-terminally truncated TPPP/p25 shows a lower Bmax for microtubule binding, suggesting that it may bind to a site of tubulin that is masked in microtubules. Bimolecular fluorescent complementation assays in cells expressing combinations of various TPPP/p25 fragments, but not that of the central folded domain, resulted in the generation of a fluorescence signal colocalized with perinuclear microtubule bundles insensitive to microtubule inhibitors. The data suggest that the central folded domain of TPPP/p25 following binding to microtubules can drive s homotypic protein-protein interactions leading to bundled microtubules.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2015, 5, pp.13242
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Soumis le : mardi 15 septembre 2015 - 08:30:15
Dernière modification le : lundi 19 février 2018 - 14:34:03

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Salvatore Debonis, Emmanuelle Neumann, Dimitrios Skoufias. Self protein-protein interactions are involved in TPPP/p25 mediated microtubule bundling.. Scientific Reports, Nature Publishing Group, 2015, 5, pp.13242. 〈hal-01199159〉



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