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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere66491
JournaleLife
Volume10
DOIs
StatePublished - Jun 2021

Keywords

  • Cytoskeleton
  • Inhibitory neurons
  • K channels
  • Perineuronal net
  • Scaffolding protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'Ankyrin-r regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K<sup>+</sup> channels'. Together they form a unique fingerprint.

Cite this