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

Stevens, S.; Longley, C. M.; Ogawa, Y.; Teliska, L.; Arumanayagam, A.; Nair, S.; Oses-Prieto, J. A.; Burlingame, A. L.; Cykowski, M.; Xue, M.; Rasband, M. N.

doi:10.1101/2021.01.21.427626

bioRxiv · 10.1101/2021.01.21.427626

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

Stevens, S.·Longley, C. M.·Ogawa, Y.·Teliska, L.·Arumanayagam, A.·Nair, S.·Oses-Prieto, J. A.·Burlingame, A. L.·Cykowski, M.·Xue, M.·Rasband, M. N.

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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 {beta}1 spectrin-based cytoskeleton.

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Stevens, S., Longley, C. M., Ogawa, Y., Teliska, L., Arumanayagam, A., Nair, S., Oses-Prieto, J. A., Burlingame, A. L., Cykowski, M., Xue, M., Rasband, M. N.. 2021-01-21. Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels. https://doi.org/10.1101/2021.01.21.427626

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