TY - JOUR

T1 - An ankyrin G–binding motif mediates TRAAK periodic localization at axon initial segments of hippocampal pyramidal neurons

AU - Luque-Fernández, Virginia

AU - Vanspauwen, Sam K.

AU - Landra-Willm, Arnaud

AU - Arvedsen, Emil

AU - Besquent, Maïlys

AU - Rasmussen, Hanne B.

AU - Sandoz, Guillaume

N1 - Publisher Copyright: Copyright © 2024 the Author(s).

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - ankyrin G

KW - axon initial segment

KW - K2P4.1

KW - KCNK4

KW - STED

U2 - 10.1073/pnas.2310120121

DO - 10.1073/pnas.2310120121

M3 - Journal article

C2 - 39058579

AN - SCOPUS:85199723948

VL - 121

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 31

M1 - e2310120121

ER -