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Published in: Acta Neuropathologica Communications 1/2015

Open Access 01-12-2015 | Research

Tau phosphorylation regulates the interaction between BIN1’s SH3 domain and Tau’s proline-rich domain

Authors: Yoann Sottejeau, Alexis Bretteville, François-Xavier Cantrelle, Nicolas Malmanche, Florie Demiaute, Tiago Mendes, Charlotte Delay, Harmony Alves Dos Alves, Amandine Flaig, Peter Davies, Pierre Dourlen, Bart Dermaut, Jocelyn Laporte, Philippe Amouyel, Guy Lippens, Julien Chapuis, Isabelle Landrieu, Jean-Charles Lambert

Published in: Acta Neuropathologica Communications | Issue 1/2015

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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’s SH3 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.
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Metadata
Title
Tau phosphorylation regulates the interaction between BIN1’s SH3 domain and Tau’s proline-rich domain
Authors
Yoann Sottejeau
Alexis Bretteville
François-Xavier Cantrelle
Nicolas Malmanche
Florie Demiaute
Tiago Mendes
Charlotte Delay
Harmony Alves Dos Alves
Amandine Flaig
Peter Davies
Pierre Dourlen
Bart Dermaut
Jocelyn Laporte
Philippe Amouyel
Guy Lippens
Julien Chapuis
Isabelle Landrieu
Jean-Charles Lambert
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-015-0237-8

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