An ankyrin G–binding motif mediates TRAAK periodic localization at axon initial segments of hippocampal pyramidal neurons

Virginia Luque-Fernández, Sam K. Vanspauwen, Arnaud Landra-Willm, Emil Arvedsen, Maïlys Besquent, Hanne B. Rasmussen*, Guillaume Sandoz

*Corresponding author for this work

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Abstract

The axon initial segment (AIS) is a critical compartment in neurons. It converts post-synaptic input into action potentials that subsequently trigger information transfer to target neurons. This process relies on the presence of several voltage-gated sodium (NaV) and potassium (KV) channels that accumulate in high densities at the AIS. TRAAK is a mechanosensitive leak potassium channel that was recently localized to the nodes of Ranvier. Here, we uncover that TRAAK is also present in AISs of hippocampal and cortical neurons in the adult rat brain as well as in AISs of cultured rat hippocampal neurons. We show that the AIS localization is driven by a C-terminal ankyrin G–binding sequence that organizes TRAAK in a 190 nm spaced periodic pattern that codistributes with periodically organized ankyrin G. We furthermore uncover that while the identified ankyrin G–binding motif is analogous to known ankyrin G–binding motifs in NaV1 and KV7.2/KV7.3 channels, it was acquired by convergent evolution. Our findings identify TRAAK as an AIS ion channel that convergently acquired an ankyrin G–binding motif and expand the role of ankyrin G to include the nanoscale organization of ion channels at the AIS.

Original languageEnglish
Article numbere2310120121
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number31
Number of pages11
ISSN0027-8424
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 the Author(s).

Keywords

  • ankyrin G
  • axon initial segment
  • K2P4.1
  • KCNK4
  • STED

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