Study On The Expression And Transcriptional Regulation Of Juxtanodin And Identification And Characterization For HErmin

Oligodendrocyte is mainly a myelin-forming cell which extends many processes to contact and repeatedly envelopes the stretch of axon to form myelin. The unique composition of myelin and its unique segmental structure responsible for the saltatory conduction of nerve impulses allow the myelin sheath to support the fast nerve conduction in the thin fibers in the vertebrate system. In addition, oligodendrocyte plays important roles in the regeneration of neuron and the growth of axons. The process of myelin formation depends on myelin-specific proteins expressed sequentially in the development of oligodendrocyte. Therefore study the transcriptional regulation and expression of these genes could help us to further understand the rules in the oligodendrocyte development and support more information for diagnosis and treatment of demyelination disease.Juxtanodin(JN) was identified as an oligodendrocyte-specific protein expressed at late stage of maturation of oligodendrocyte and is involved in myelination. In oligodendrocyte, JN could promote the formation of filopodia through binding with F-actin and colocalized with another myelin-specific protein-CNPase. Other fuctions of JN, however, are still unknown.Through immunohistochemistry we systematically analyzed the expression and distribution of JN in rat central nervous system (CNS). The results showed that JN emerged at P7 in corpus callosum in forebrain and reached its peak at P28 while in spinal cord, JN signal was detected as early as P0 and reached its peak at P14. To investigate the transcriptional regulation mechanisms of JN, we cloned its promoter and identified its core promoter region. The in vitro results showed that this promoter exhibits at least partially glia-specific properties. Next we demonstrated the up-regulation of the JN promoter by ATRA/Nkx2.2 in C6 cells. In addition, we used in vivo electroporation to transfect the promoter region of JN into the lateral ventricle of rats pups at P0 and further confirmed the promoter activity.We identified hErmin, a putative homologous protein of JN, in human brain. The immunofluorescence results showed that hErmin colocalized with two myelin-specific proteins, CNPase and MBP, in cell bodies and process. No significant hErmin colocalization was found with glial fibrillary acidic protein (GFAP)in astrocytes, or neurofilament 200 (NF-200) in neurons. These results showed that hErmin is an novel oligodendrocyte-specific protein and may be involved in the formation of myelin. Further we demonstrated that hErmin could induce great morphology changes in transfected cells through binding with F-actin, suggesting that hErmin is a cytoskeleton protein. All work mentioned above may provide useful information for the study of development of oligodendrocyte and the formation of myelin during the maturation of CNS.