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

• Published in: eLife 2021-06, Vol.10
• Main Authors: Stevens, Sharon R, Longley, Colleen M, Ogawa, Yuki, Teliska, Lindsay H, Arumanayagam, Anithachristy S, Nair, Supna, Oses-Prieto, Juan A, Burlingame, Alma L, Cykowski, Matthew D, Xue, Mingshan, Rasband, Matthew N
• Format: Article
• Language: English
• Subjects: Brain; Cytoskeletal proteins; Membrane proteins; Neurons; Scientific equipment and supplies industry
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.66491

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.sup.+ 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.sup.+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K.sup.+ 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.sup.+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying [beta]1 spectrin-based cytoskeleton.