LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period.
J Cell Biol
; 222(4)2023 04 03.
Article
em En
| MEDLINE
| ID: mdl-36828548
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Proteínas ADAM
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Bainha de Mielina
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Proteínas do Tecido Nervoso
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2023
Tipo de documento:
Article