title: Tau phosphorylation regulates the interaction between BIN1's SH3 domain and Tau's proline-rich domain.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Sottejeau
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.affiliation: Université de Lille, Lille, France.|CNRS, UMR 8576,, Lille, France.|FraBio IR 3688, Lille, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Cantrelle
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Malmanche
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Florie
authors.initials: F
authors.lastname: Demiaute
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Tiago
authors.initials: T
authors.lastname: Mendes
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Delay
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Harmony
authors.initials: H
authors.lastname: Alves Dos Alves
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Flaig
authors.affiliation: Litwin-Zucker Research Center, Feinstein Institute for Medical Research, North-Shore Long Island Jewish Health System, Manhasset, NY, USA.|Albert Einstein College of Medicine of Yeshiva University, New York, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dourlen
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.|Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Dermaut
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, Université de Strasbourg, Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: Université de Lille, Lille, France.|CNRS, UMR 8576,, Lille, France.|FraBio IR 3688, Lille, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.affiliation: INSERM, UMR 1167, Lille, France.|Institut Pasteur de Lille, Lille, France.|Université de Lille, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Chapuis
authors.affiliation: Université de Lille, Lille, France. isabelle.landrieu@univ-lille1.fr.|CNRS, UMR 8576,, Lille, France. isabelle.landrieu@univ-lille1.fr.|FraBio IR 3688, Lille, France. isabelle.landrieu@univ-lille1.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.affiliation: INSERM, UMR 1167, Lille, France. jean-charles.lambert@pasteur-lille.fr.|Institut Pasteur de Lille, Lille, France. jean-charles.lambert@pasteur-lille.fr.|Université de Lille, Lille, France. jean-charles.lambert@pasteur-lille.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011392:Proline / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains / Q000502:physiology*; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D016875:tau Proteins; D011392:Proline