Self protein-protein interactions are involved in TPPP/p25 mediated microtubule bundling.
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.
Université de Grenoble Alpes, F-38044 Grenoble, France.|CNRS, F-38044 Grenoble, France.|CEA, IBS, F-38044 Grenoble, France.
Salvatore
S
DeBonis
Université de Grenoble Alpes, F-38044 Grenoble, France.|CNRS, F-38044 Grenoble, France.|CEA, IBS, F-38044 Grenoble, France.
Emmanuelle
E
Neumann
Université de Grenoble Alpes, F-38044 Grenoble, France.|CNRS, F-38044 Grenoble, France.|CEA, IBS, F-38044 Grenoble, France.
Dimitrios A
DA
Skoufias
D000818:Animals; D002417:Cattle; D005453:Fluorescence; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017384:Sequence Deletion
D009419:Nerve Tissue Proteins; C118136:TPPP protein, human; D017239:Paclitaxel