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Cytoskeleton in myelin-basic-protein-deficient shiverer oligodendrocytes
C A Dyer1, T M Philibotte, S Billings-Gagliardi
1Department of Biomedical Sciences, E.K. Shriver Center, Waltham, Mass. 02254, USA.
Abstract:
Production of CNS myelin by oligodendrocytes requires the regulated synthesis and assembly of cytoskeletal components. However, the molecular signals that mediate this process are not known. Here we use the shiverer mutant mouse, which is missing a large segment of the myelin basic protein (MBP) gene, to investigate the possible role in cytoskeletal assembly of an MBP gene product or of other myelin components whose expression may be linked to that of MBP. In axon-free cultures, we find that approximately half of shiverer oligodendrocytes have enlarged cell bodies, abnormal processes and fail to elaborate extensive membrane sheets. In those membrane sheets that are elaborated by shiverer oligodendrocytes, microtubular structures are abnormal in size and distribution. Additionally, 2',3'-cyclic nucleotide 3'-phosphohydrolase and microfilaments are not colocalized with microtubular structures as they would be in mature wild-type membrane sheets. These observations suggest that an MBP gene product has a direct or indirect role in regulating various aspects of cytoskeleton assembly in wild-type oligodendrocytes. In the absence of this signal, oligodendrocytes apparently do not normally assemble cytoskeleton; this may be one important basis for the abnormal morphology of intact shiverer CNS.
Insights
The myelin basic protein (MBP) gene product is crucial for oligodendrocyte cytoskeleton assembly. Its absence in shiverer mice leads to abnormal cell structures and impaired myelin production in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Oligodendrocytes produce CNS myelin through regulated synthesis and assembly of cytoskeletal components.
- The molecular signals governing this process are largely unknown.
- The myelin basic protein (MBP) gene is essential for myelin sheath formation.
Purpose of the Study:
- To investigate the role of MBP gene products in oligodendrocyte cytoskeletal assembly.
- To explore potential links between MBP expression and other myelin components.
- To understand the basis of abnormal CNS morphology in shiverer mutant mice.
Main Methods:
- Utilized shiverer mutant mice lacking a large segment of the MBP gene.
- Examined oligodendrocytes in axon-free cultures.
- Analyzed microtubular structures, microfilaments, and 2',3'-cyclic nucleotide 3'-phosphohydrolase localization within membrane sheets.
Main Results:
- Approximately 50% of shiverer oligodendrocytes exhibited enlarged cell bodies and abnormal processes.
- Shiverer oligodendrocytes failed to form extensive membrane sheets, and those formed had abnormal microtubular structures.
- Key myelin components like 2',3'-cyclic nucleotide 3'-phosphohydrolase and microfilaments were mislocalized in shiverer oligodendrocytes.
Conclusions:
- An MBP gene product plays a direct or indirect role in regulating oligodendrocyte cytoskeleton assembly.
- The absence of this MBP-related signal disrupts normal cytoskeletal organization.
- This cytoskeletal defect is a significant contributor to the abnormal CNS morphology observed in shiverer mutant mice.