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

作者：Sharon R. Stevens, Colleen M Longley, Yuki Ogawa, Lindsay H. Teliska, Anithachristy S. Arumanayagam, Supna Nair, Juan A. Osés-Prieto, Alma L. Burlingame, Matthew D. Cykowski, Mingshan Xue, Matthew N. Rasband · 发表于：eLife · 年份：2021 · DOI：10.7554/elife.66491 · 被引用次数：56 · 研究领域：Erythrocyte Function and Pathophysiology、Receptor Mechanisms and Signaling、Ion channel regulation and function

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.