LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period
Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon-glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function...
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| Veröffentlicht in: | The Journal of cell biology 2023-04, Vol.222 (4), p.1 |
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| creator | Kozar-Gillan, Nina Velichkova, Atanaska Kanatouris, George Eshed-Eisenbach, Yael Steel, Gavin Jaegle, Martine Aunin, Eerik Peles, Elior Torsney, Carole Meijer, Dies N |
| description | Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon-glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. Our findings not only reveal a previously unknown molecular pathway that regulates Kv1 channel clustering, but they also demonstrate that the juxtaparanodal Kv1 channels that are concealed below the myelin sheath, play a significant role in modifying axonal physiology. |
| doi_str_mv | 10.1083/jcb.202211031 |
| format | Article |
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However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. Our findings not only reveal a previously unknown molecular pathway that regulates Kv1 channel clustering, but they also demonstrate that the juxtaparanodal Kv1 channels that are concealed below the myelin sheath, play a significant role in modifying axonal physiology.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.202211031</identifier><identifier>PMID: 36828548</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Action Potentials ; ADAM Proteins - metabolism ; Adhesion ; Axons ; Axons - metabolism ; Cell Adhesion Molecules, Neuronal - metabolism ; Cell Signaling ; Channels ; Clustering ; Development ; Firing rate ; Myelin ; Myelin Sheath - metabolism ; Nerve Tissue Proteins - metabolism ; Neuroglia - metabolism ; Neuroscience ; Nodes of Ranvier ; Potassium ; Potassium channels (voltage-gated) ; Potassium Channels, Voltage-Gated - metabolism ; Ranvier's Nodes - metabolism ; Refractory period ; Sheaths</subject><ispartof>The Journal of cell biology, 2023-04, Vol.222 (4), p.1</ispartof><rights>2023 Kozar-Gillan et al.</rights><rights>Copyright Rockefeller University Press Apr 2023</rights><rights>2023 Kozar-Gillan et al. 2023 Kozar-Gillan et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-72a5acb520c06e237205f7ac5dd1185b2b7c5f1ff0c7da06f9ff5374c3fcabd43</citedby><cites>FETCH-LOGICAL-c415t-72a5acb520c06e237205f7ac5dd1185b2b7c5f1ff0c7da06f9ff5374c3fcabd43</cites><orcidid>0000-0002-3434-7884 ; 0000-0001-8385-2636 ; 0000-0002-6941-1188 ; 0000-0002-3325-0597 ; 0000-0002-2448-3364 ; 0000-0003-4785-986X ; 0000-0002-8461-6341 ; 0000-0002-5831-0605 ; 0000-0002-2154-6518 ; 0000-0001-6102-4987</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36828548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kozar-Gillan, Nina</creatorcontrib><creatorcontrib>Velichkova, Atanaska</creatorcontrib><creatorcontrib>Kanatouris, George</creatorcontrib><creatorcontrib>Eshed-Eisenbach, Yael</creatorcontrib><creatorcontrib>Steel, Gavin</creatorcontrib><creatorcontrib>Jaegle, Martine</creatorcontrib><creatorcontrib>Aunin, Eerik</creatorcontrib><creatorcontrib>Peles, Elior</creatorcontrib><creatorcontrib>Torsney, Carole</creatorcontrib><creatorcontrib>Meijer, Dies N</creatorcontrib><title>LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon-glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. Our findings not only reveal a previously unknown molecular pathway that regulates Kv1 channel clustering, but they also demonstrate that the juxtaparanodal Kv1 channels that are concealed below the myelin sheath, play a significant role in modifying axonal physiology.</description><subject>Action Potentials</subject><subject>ADAM Proteins - metabolism</subject><subject>Adhesion</subject><subject>Axons</subject><subject>Axons - metabolism</subject><subject>Cell Adhesion Molecules, Neuronal - metabolism</subject><subject>Cell Signaling</subject><subject>Channels</subject><subject>Clustering</subject><subject>Development</subject><subject>Firing rate</subject><subject>Myelin</subject><subject>Myelin Sheath - metabolism</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neuroglia - metabolism</subject><subject>Neuroscience</subject><subject>Nodes of Ranvier</subject><subject>Potassium</subject><subject>Potassium channels (voltage-gated)</subject><subject>Potassium Channels, Voltage-Gated - metabolism</subject><subject>Ranvier's Nodes - metabolism</subject><subject>Refractory period</subject><subject>Sheaths</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1PGzEQhi1U1KTQI9dqpV64LBl_TLx7qRRRSqMGcYGz5fXasNHGTu1d1Px7HIVGpSePZx698_ESckHhikLFZ2vTXDFgjFLg9IRMKQooKyrgA5kCMFrWyHBCPqW0BgAhBf9IJnxesQpFNSV6dbvkM1Yuvi_uGC86P9iozdAFnwrTjyl_i18vtDDP2nvbp0wUm53tO68H2xb6zx4cQhHt09jnVA7cXiDEXbG1sQvtOTl1uk_289t7Rh5_3Dxc_yxX97fL68WqNILiUEqmUZsGGRiYW8YlA3RSG2xbSitsWCMNOuocGNlqmLvaOeRSGO6MblrBz8i3g-52bDa2NdYPUfdqG7uNjjsVdKfeV3z3rJ7Ci6rrWiLILHD5JhDD79GmQW26ZGzfa2_DmBSTFYAUgPteX_9D12GMPq-XqRpR4JxBpsoDZWJIKR_mOAwFtTdPZfPU0bzMf_l3gyP91y3-Cnw7lcc</recordid><startdate>20230403</startdate><enddate>20230403</enddate><creator>Kozar-Gillan, Nina</creator><creator>Velichkova, Atanaska</creator><creator>Kanatouris, George</creator><creator>Eshed-Eisenbach, Yael</creator><creator>Steel, Gavin</creator><creator>Jaegle, Martine</creator><creator>Aunin, Eerik</creator><creator>Peles, Elior</creator><creator>Torsney, Carole</creator><creator>Meijer, Dies N</creator><general>Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3434-7884</orcidid><orcidid>https://orcid.org/0000-0001-8385-2636</orcidid><orcidid>https://orcid.org/0000-0002-6941-1188</orcidid><orcidid>https://orcid.org/0000-0002-3325-0597</orcidid><orcidid>https://orcid.org/0000-0002-2448-3364</orcidid><orcidid>https://orcid.org/0000-0003-4785-986X</orcidid><orcidid>https://orcid.org/0000-0002-8461-6341</orcidid><orcidid>https://orcid.org/0000-0002-5831-0605</orcidid><orcidid>https://orcid.org/0000-0002-2154-6518</orcidid><orcidid>https://orcid.org/0000-0001-6102-4987</orcidid></search><sort><creationdate>20230403</creationdate><title>LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period</title><author>Kozar-Gillan, Nina ; 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However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. 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| subjects | Action Potentials ADAM Proteins - metabolism Adhesion Axons Axons - metabolism Cell Adhesion Molecules, Neuronal - metabolism Cell Signaling Channels Clustering Development Firing rate Myelin Myelin Sheath - metabolism Nerve Tissue Proteins - metabolism Neuroglia - metabolism Neuroscience Nodes of Ranvier Potassium Potassium channels (voltage-gated) Potassium Channels, Voltage-Gated - metabolism Ranvier's Nodes - metabolism Refractory period Sheaths |
| title | LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period |
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