Interaction between the guanylate kinase domain of PSD-95 and the proline-rich region and microtubule binding repeats 2 and 3 of tau

Emmanuel Prikas, Holly Ahel, Kristie Stefanoska, Prita Riana Asih, Alexander Volkerling, Lars M. Ittner, Arne Ittner

Research output: Contribution to journalArticlepeer-review

Abstract

The microtubule-associated protein tau is a key factor in neurodegenerative proteinopathies and is predominantly found in the neuronal axon. However, somatodendritic localization of tau occurs for a subset of pathological and physiologic tau. Dendritic tau can localize to post-synapses where it interacts with proteins of the post-synaptic density (PSD) protein PSD-95, a membrane-associated guanylate kinase (MAGUK) scaffold factor for organization of protein complexes within the PSD, to mediate downstream signals. The sub-molecular details of this interaction, however, remain unclear. Here, we use interaction mapping in cultured cells to demonstrate that tau interacts with the guanylate kinase (GUK) domain in the C-terminal region of PSD-95. The PSD-95 GUK domain is required and sufficient for a complex with full-length human tau. Mapping the interaction of the MAGUK core on tau revealed the microtubule binding repeats 2 and 3 and the proline-rich region contribute to this interaction, while the N- and C-terminal regions of tau inhibit interaction. These results reveal intramolecular determinants of the protein complex of tau and PSD-95 and increase our understanding of tau interactions regulating neurotoxic signaling at the molecular level.
Original languageEnglish
Number of pages26
JournalInternational Journal of Biochemistry and Cell Biology
Early online date1 Apr 2021
DOIs
Publication statusE-pub ahead of print - 1 Apr 2021

Keywords

  • microtubule-associated protein tau
  • membrane-associated guanylate kinase
  • MAGUK
  • PSD-95
  • interaction
  • protein complex
  • binding site
  • interaction mapping

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