A KCNC1 variant linked to Rett syndrome disrupts ER to Golgi trafficking of Kv3.1 channel

• 成果类型: Article
• 署名作者: Maureira, Diego; Rubilar, Carla; Lopez, Joaquin; Santander, Paola; Moldenhauer, Hans; Silva, Ian; Cruz, Pablo; Riquelme, Denise; Baeza, Javiera; Gonzalez, Wendy; Orioi, Patricio; Servili, Evrim; Troncoso, Monica; Leiva-Salcedog, Elias; Cerdaa, Oscar
• 署名单位: Universidad de Chile; Universidad de Chile; Universidad de Chile; Universidad Santo Tomas; Universidad Mayor; Universidad de Santiago de Chile; Universidad de Talca; Universidad de Valparaiso
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2424514123
• 发表日期: 2026-03-17
• 页码: e2424514123
• 关键词: KCNC1; Rett syndrome; channelopathy; ion channel trafficking; GATED K+ CHANNELS; potassium channel; PHARMACOLOGICAL CHARACTERIZATION; Mutation; dysfunction; expression; genetics; epilepsy; spiking; subunit

摘要

Intrinsic neuronal excitability, defined by the balance between input and output signals, is crucial to neural function, and its disruption underlies various neurological diseases. Kv3.1 channels, encoded by KCNC1, are essential for high-frequency action potential firing. Variants in these channels are associated with several subtypes of epilepsy. We report a patient with developmental regression and epilepsy, meeting Rett syndrome criteria, ence in the plasma membrane and is retained in the endoplasmic reticulum. In murine firing frequency and exclusion of the channel from the axon initial segment. Consistently, we found a decreased firing frequency using a conductance-based computational neuronal model. In summary, this study identifies a link between a KCNC1 variant and Rett syndrome, highlighting the importance of S474 residue in Kv3.1 channel trafficking and function in neurons.