LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to fine-tune axonal properties

Nina Kozar-Gillan, Atanaska Velichkova, George Kanatouris, Yael Eshed-Eisenbach, Gavin Steel, Martine Jaegle, Eerik Aunin, Elior Peles, Carole Torsney, Dies N. Meijer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon–glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. Our findings not only reveal a previously unknown molecular pathway that regulates Kv1 channel clustering, but they also demonstrate that the juxtaparanodal Kv1 channels that are concealed below the myelin sheath, play a significant role in modifying axonal physiology.
Original languageEnglish
Article numbere202211031
Number of pages21
JournalJournal of Cell Biology
Issue number4
Publication statusPublished - 24 Feb 2023


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