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- Title
Tau phosphorylation regulates the interaction between BIN1's SH3 domain and Tau's proline-rich domain.
- Authors
Sottejeau, Yoann; Bretteville, Alexis; Cantrelle, François-Xavier; Malmanche, Nicolas; Demiaute, Florie; Mendes, Tiago; Delay, Charlotte; Alves, Harmony Alves Dos; Flaig, Amandine; Davies, Peter; Dourlen, Pierre; Dermaut, Bart; Laporte, Jocelyn; Amouyel, Philippe; Lippens, Guy; Chapuis, Julien; Landrieu, Isabelle; Lambert, Jean-Charles
- Abstract
Introduction: The application of high-throughput genomic approaches has revealed 24 novel risk loci for Alzheimer's disease (AD). We recently reported that the bridging integrator 1 (BIN1) risk gene is linked to Tau pathology. Results: We used glutathione S-transferase pull-down assays and nuclear magnetic resonance (NMR) experiments to demonstrate that BIN1 and Tau proteins interact directly and then map the interaction between BIN1'sS H 3 domain and Tau's proline-rich domain (PRD) . Our NMR data showed that Tau phosphorylation at Thr231 weakens the SH3-PRD interaction. Using primary neurons, we found that BIN1-Tau complexes partly co-localize with the actin cytoskeleton; however, these complexes were not observed with Thr231-phosphorylated Tau species. Conclusion: Our results show that (i) BIN1 and Tau bind through an SH3-PRD interaction and (ii) the interaction is downregulated by phosphorylation of Tau Thr231 (and potentially other residues). Our study sheds new light on regulation of the BIN1/Tau interaction and opens up new avenues for exploring its complex's role in the pathogenesis of AD.
- Subjects
TAU proteins; PHOSPHORYLATION; GENETICS of Alzheimer's disease
- Publication
Acta Neuropathologica Communications, 2015, Vol 3, Issue 1, p1
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-015-0237-8