Lgi1 promotes the peripheral nervous system myelination via controlling myelin sheath assembling and TSC1-mTOR dependent lipid biosynthesis
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.
国家科技期刊平台
NSTL
万方数据
维普
