Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels
- Baylor College of Medicine, United States
- Houston Methodist Hospital, United States
- University of California, San Francisco, United States
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 b1 spectrin-based cytoskeleton.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.
Article and author information
Author details
Juan A Oses-Prieto
Funding
National Institute of Neurological Disorders and Stroke (NS044916)
- Matthew N Rasband
National Institute of General Medical Sciences (GM103481)
- Alma L Burlingame
National Institute of Mental Health (MH117089)
- Mingshan Xue
National Institute of Neurological Disorders and Stroke (NS100893)
- Mingshan Xue
National Institute of Neurological Disorders and Stroke (NS100300)
- Sharon Stevens
National Institute of Mental Health (MH118804)
- Colleen M Longley
National Institute of Neurological Disorders and Stroke (NS118584)
- Matthew Cykowski
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Alma L Burlingame
- Matthew N Rasband
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were conducted in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee at Baylor College of Medicine under approval AN4634.
Copyright
© 2021, Stevens et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels
eLife 10:e66491.
https://doi.org/10.7554/eLife.66491
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