遵义医科大学学报2024，Vol.47Issue(1)：10-17,8.
Lgi1基因通过控制髓鞘装配和TSC1-mTORC1依赖的脂质生物合成促进外周神经系统髓鞘化
Lgi1 promotes the peripheral nervous system myelination via controlling myelin sheath assembling and TSC1-mTOR dependent lipid biosynthesis
摘要
Abstract
Objective To investigate the function of leucine-rich glioma inactivated 1(Lgi1)and its molecular mechanism in the myelination of the peripheral nervous system(PNS).Methods Western blotting was used to monitor the expression of Lgi1 and myelin-related proteins in the SN group(sciatic nerve)at postnatal day P3-P60,Brain group(brain)at postnatal day P0-P180,SN and Brain groups after knocking out Lgi1 during postna-tal development,and to further investigate the mechanism of Lgi1 on PNS myelination and to detect the changes of Laminin-integrin signaling and TSC1-mTOC1 pathway in Lgi1-/-mice.Immunohistochemistry and electron mi-croscopy(EM)were used to examine the changes in myelin-related proteins and the ultrastructural changes of myelin sheath in Lgi1 deficient mice.Results Western blotting revealed that deletion of Lgi1 caused decreased expression level of myelin-associated proteins[Myelin basic protein(MBP),Myelin oligodendrocyte glycoprotein(MOP),Myelin-associated glycoprotein(MAP),and Myelin protein zero(MPZ)]in the PNS(P＜0.05).Immunohistochemistry and EM revealed an increased number of unmyelinated axons in the SN of Lgi1-/-mice.EM data also showed that the g-ratio and unfolded myelin sheath were increased in Lgi1-/-PNS.Laminin,inte-grin-1β,and integrin-4β were detected in the SN of Lgi1-/-mice using western blotting,and the results showed a significant decrease in protein expression and an increase in integrin-1 α expression(P＜0.05).Additionally,immunofluorescence showed less MBP co-staining with Laminin.Furthermore,lower FASN level and unbalanced TSC1-mTORC1 activity were shown by western blotting in Lgi1-/-mice.Conclusion Through Laminin-integrin signaling and the TSC1-mTORC1 dependent lipid biosynthesis,the Lgi1 gene is involved in controlling the process of PNS myelination.关键词
富亮氨酸胶质瘤失活基因1/髓鞘化/髓鞘装配/脂质合成/雷帕霉素靶蛋白Key words
leucine rich glioma inactivated 1/myelination/myelin sheath assembling/lipid biosynthesis/mammalian target of rapamycin分类
医药卫生引用本文复制引用
唐涣垚,易如岚,梁小玲,王旭,冉啟鹏,周亮..Lgi1基因通过控制髓鞘装配和TSC1-mTORC1依赖的脂质生物合成促进外周神经系统髓鞘化[J].遵义医科大学学报,2024,47(1):10-17,8.基金项目
国家自然科学基金资助项目(NO:82060224) （NO:82060224）
贵州省科技计划项目[NO:黔科合基础(2020)1Y088] （2020）
遵义市科技局联合基金项目[NO:遵市科合HZ字(2021)194号]. （2021）
