The major function of the oligodendrocyte in the CNS is to produce myelin, the membrane sheath that envelops axons and is necessary for saltatory conduction. Our long term goal is to elucidate the process of myelination and its regulation. Myelin basic protein (MBP), a major structural component of the sheath, is essential for the formation of myelin. MBP is synthesized at its site of assembly in the myelin membrane. This is accomplished by transport of MBP mRNA from the nucleus to the cell body and down the cell processes and into the myelin sheath, followed by anchoring and translation. The short term goal of our research efforts is to elucidate this trafficking pathway. This will be accomplished by: Characterizing the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2, the essential trans-acting factor that recognizes the signal sequence for transport present in MBP mRNA; identifying other constituents of the MBP mRNA trafficking system and determining their role; characterizing the conditions under which MBP mRNA trafficking is blocked or enhanced, and delineating the steps in MBP mRNA translocation from the nucleus to the myelin membrane and pattern of regulation. Microinjection of live cell in culture, confocal microscopy, immunocytochemistry, Western blot, yeast two-hybrid system, co-immunoprecipitation and subcellular fractionation procedures will be used. Hypomyelination and demyelination have severe neurological consequences. Understanding the mechanism of mRNA trafficking is the first step in understanding how myelin is made a repaired throughout the life of an individual. This knowledge should lead to therapies, immunochemical or pharmaceutical for patients afflicted with demyelinating diseases of the CNS and PNS such as multiple sclerosis, Charcot-Marie-Tooth disease and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and chemotherapy or viral infections.
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| Giampetruzzi, Anthony; Carson, John H; Barbarese, Elisa (2013) FMRP and myelin protein expression in oligodendrocytes. Mol Cell Neurosci 56:333-41 |
| Tatavarty, Vedakumar; Ifrim, Marius F; Levin, Mikhail et al. (2012) Single-molecule imaging of translational output from individual RNA granules in neurons. Mol Biol Cell 23:918-29 |
| Han, Siew Ping; Friend, Lexie R; Carson, John H et al. (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic 11:886-98 |
| Carson, John H; Gao, Yuanzheng; Tatavarty, Vedakumar et al. (2008) Multiplexed RNA trafficking in oligodendrocytes and neurons. Biochim Biophys Acta 1779:453-8 |
| Kosturko, Linda D; Maggipinto, Michael J; Korza, George et al. (2006) Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs. Mol Biol Cell 17:3521-33 |
| Kosturko, Linda D; Maggipinto, Michael J; D'Sa, Chrystal et al. (2005) The microtubule-associated protein tumor overexpressed gene binds to the RNA trafficking protein heterogeneous nuclear ribonucleoprotein A2. Mol Biol Cell 16:1938-47 |
| Carson, John H; Barbarese, Elisa (2005) Systems analysis of RNA trafficking in neural cells. Biol Cell 97:51-62 |
| Maggipinto, M; Rabiner, C; Kidd, G J et al. (2004) Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation. J Neurosci Res 75:614-23 |
| Shan, Jianguo; Munro, Trent P; Barbarese, Elisa et al. (2003) A molecular mechanism for mRNA trafficking in neuronal dendrites. J Neurosci 23:8859-66 |
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