Truncated Tau with the Fyn-binding domain and without the microtubule-binding domain hinders the myelinating capacity of an oligodendrocyte cell line.
The mechanisms underlying developmental myelination have therapeutic potential following CNS injury and degeneration. We report that transplanted central glial (CG)-4 cells had a diminished myelinating capacity in myelin-deficient (md) rats when cells express a mutated form of Tau (Tau [688]), which binds Fyn but not the microtubules. In the brain of the md rats, Tau [688]-transfected CG-4 cells displayed a decrease in cellular process outgrowth and myelination; in the spinal cord the extent of myelination rostral and caudal to the injection site was decreased. In contrast, control Tau [605]-transfected CG-4 cells formed long cellular processes and substantial areas of myelin both in the brain and spinal cord. In culture, Tau [688]-transfected CG-4 cells displayed a decrease in cellular process outgrowth, and Fyn localized largely in the cell body, not the processes. Thus, Tau in oligodendrocytes plays a key role in myelination, and a functional Tau-Fyn interaction might have therapeutic potential during demyelination and myelin repair following CNS injury and degeneration.
Belkadi
Abdelmadjid
A
Department of Medical Science, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
LoPresti
Patrizia
P
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002461:Cell Line, Transformed; D017690:Cell Transplantation / Q000379:methods; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D013119:Spinal Cord Injuries / Q000601:surgery; D014162:Transfection / Q000379:methods; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016875:tau Proteins; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn