OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation

• 成果类型: Article
• 署名作者: Teng, Xiao-Yu; Hu, Ping; Zhang, Cai-Ming; Zhang, Qin-Xin; Yang, Guolin; Zang, Yan-Yu; Liu, Zhi-Xiong; Chen, Guiquan; Shi, Yun Stone
• 署名单位: Nanjing University; Nanjing Medical University; Southern Medical University - China
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12089
• DOI: 10.1073/pnas.2403652121
• 发表日期: 2024-08-06
• 关键词: white-matter; myelination; epilepsy; inactivation; regulator

摘要

a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding followed by mass spectrometry. An OL- specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further contrast, re- expression of LGI1- unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on