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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The microtubule-associated protein tau is a key factor in neurodegenerative proteinopathies and is predominantly found in neuronal axons. However, somatodendritic localization of tau occurs in a subset of pathological and physiological 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. However, the molecular details of this interaction remain unclear. Here, we used 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 for a complex with full-length human tau. Mapping the interaction of the MAGUK core with tau revealed that the microtubule binding repeats 2 and 3 and the proline-rich region contributes to this interaction, while the N- and C-terminal regions of tau inhibit interaction. These results reveal the 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
Pages (from-to)606-616
Number of pages11
JournalBiochemistry and Cell Biology
Volume99
Issue number5
DOIs
Publication statusPublished - Oct 2021

Keywords

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

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