eLife (Jun 2021)

Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

  • Sharon R Stevens,
  • Colleen M Longley,
  • Yuki Ogawa,
  • Lindsay H Teliska,
  • Anithachristy S Arumanayagam,
  • Supna Nair,
  • Juan A Oses-Prieto,
  • Alma L Burlingame,
  • Matthew D Cykowski,
  • Mingshan Xue,
  • Matthew N Rasband

DOI
https://doi.org/10.7554/eLife.66491
Journal volume & issue
Vol. 10

Abstract

Read online

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv+ fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying β1 spectrin-based cytoskeleton.

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