Myelin is the multilamellar membranous sheath that surrounds axons in the CNS and the PNS, contributing to fast conduction of nerve impulses by saltatory conduction. In the CNS, the oligodendrocyte synthesizes, assembles and maintains the myelin sheath as a complex anatomical and functional structure. Each oligodendrocyte extends several dendritic processes each terminating in a myelin sheath. Myelin components are regionally distributed within the oligodendrocyte by translocation, and assembled at the site of myelin formation. The synthesis of myelin thus requires sorting mechanisms by which specific myelin components are recognized by the oligodendrocyte cellular machinery and delivered to the site of myelin assembly. This process may be regulated by neuronal signals upon interaction of an oligodendrocyte dendrite with an axon. We propose to use cell culture, genetic mutations, biochemical, immunochemical, biophysical and molecular biology techniques to study the mechanisms regulating the assembly of myelin basic protein, a major structural component of myelin, into the oligodendrocyte myelin membrane during oligodendrocyte differentiation in primary culture with neurons. Our long term objectives are to delineate the various steps in myelin morphogenesis, to determine their pattern of regulation and identify the molecular mechanisms underlying them. A better understanding of the process of myelin formation, and eventually of myelin maintenance and repair, could lead to therapies, immunochemical, pharmaceutical or genetic, for patients afflicted with demyelinating diseases of the CNS and PNS such as multiple sclerosis and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and viral infections.
| Maggipinto, Michael J; Ford, Joshay; Le, Kristine H et al. (2017) Conditional knockout of TOG results in CNS hypomyelination. Glia 65:489-501 |
| 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 |
Showing the most recent 10 out of 37 publications
