| First Author | Stefanoska K | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 10 | Pages | 3710-3719 |
| PubMed ID | 29382714 | Mgi Jnum | J:262790 |
| Mgi Id | MGI:6157250 | Doi | 10.1074/jbc.RA118.001784 |
| Citation | Stefanoska K, et al. (2018) An N-terminal motif unique to primate tau enables differential protein-protein interactions. J Biol Chem 293(10):3710-3719 |
| abstractText | Compared with other mammalian species, humans are particularly susceptible to tau-mediated neurodegenerative disorders. Differential interactions of the tau protein with other proteins are critical for mediating tau's physiological functions as well as tau-associated pathological processes. Primate tau harbors an 11-amino acid-long motif in its N-terminal region (residues 18-28), which is not present in non-primate species and whose function is unknown. Here, we used deletion mutagenesis to remove this sequence region from the longest human tau isoform, followed by glutathione S-transferase (GST) pulldown assays paired with isobaric tags for relative and absolute quantitation (iTRAQ) multiplex labeling, a quantitative method to measure protein abundance by mass spectrometry. Using this method, we found that the primate-specific N-terminal tau motif differentially mediates interactions with neuronal proteins. Among these binding partners are proteins involved in synaptic transmission (synapsin-1 and synaptotagmin-1) and signaling proteins of the 14-3-3 family. Furthermore, we identified an interaction of tau with a member of the annexin family (annexin A5) that was linked to the 11-residue motif. These results suggest that primate Tau has evolved specific residues that differentially regulate protein-protein interactions compared with tau proteins from other non-primate mammalian species. Our findings provide in vitro insights into tau's interactions with other proteins that may be relevant to human disease. |
