Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66491 |
| _version_ | 1811253315143467008 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sharon R Stevens |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:48:10Z |
| format | Article |
| id | doaj.art-7e8cf05eff984c3bb435d5a3eff36db4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:48:10Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7e8cf05eff984c3bb435d5a3eff36db42022-12-22T03:24:29ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.66491Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channelsSharon R Stevens0https://orcid.org/0000-0003-2238-8029Colleen M Longley1https://orcid.org/0000-0001-8326-6143Yuki Ogawa2Lindsay H Teliska3https://orcid.org/0000-0003-1733-6910Anithachristy S Arumanayagam4Supna Nair5https://orcid.org/0000-0001-6499-0099Juan A Oses-Prieto6https://orcid.org/0000-0003-4759-2341Alma L Burlingame7Matthew D Cykowski8Mingshan Xue9https://orcid.org/0000-0003-1463-8884Matthew N Rasband10https://orcid.org/0000-0001-8184-2477Department of Neuroscience, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United StatesDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, United StatesDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, United StatesDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, United StatesDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, United StatesDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesNeuronal 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.https://elifesciences.org/articles/66491cytoskeletonion channelperineuronal netextracellular matrixspectrinankyrin |
| spellingShingle | 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 Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels eLife cytoskeleton ion channel perineuronal net extracellular matrix spectrin ankyrin |
| title | Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels |
| title_full | Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels |
| title_fullStr | Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels |
| title_full_unstemmed | Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels |
| title_short | Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels |
| title_sort | ankyrin r regulates fast spiking interneuron excitability through perineuronal nets and kv3 1b k channels |
| topic | cytoskeleton ion channel perineuronal net extracellular matrix spectrin ankyrin |
| url | https://elifesciences.org/articles/66491 |
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