The sequestration of ion channels into molecularly distinct axonal domains is vital for nervous system function. Enrichment of voltage-gated sodium (Nav) channels to nodes of Ranvier is of considerable importance, as they function to potentiate the nerve impulse in a saltatory manner along myelinated fibers. While myelination, or the ensheathment and insulation of axons by glial cell membranes, is known to facilitate the segregation of ion channels, the exact mechanisms governing the formation, organization and stabilization of the nodes, paranodes, and juxtaparanodes remains elusive. The focus of my research is to elucidate the proteins and mechanisms regulating axonal domain organization and stabilization in mice, using a genetic approach. Understanding how these domains are coordinated, organized and maintained, will ultimately contribute to future development of therapeutic approaches for the treatment of individuals afflicted with demyelinating disorders.
Thaxton, C., Pillai, A.M., Pribisko, A.L., Dupree, J.L., and M.A. Bhat. (2011). Nodes of Ranvier Act as Barriers to Restrict Invasion of Flanking Paranodal Domains in Myelinated Axons. Neuron 69, 244-257.
Thaxton, C., Pillai, A.M., Pribisko, A.L., Labasque, M., Dupree, J.L., Faivre-Sarrailh, C., Bhat, M.A. (2010). In vivo deletion of Immunoglobulin domains 5-6 in Neurofascin (Nfasc) reveals domain specific requirements in myelinated axons. J Neurosci 30(14):4868-76.
Thaxton, C. and Bhat, M.A. (2009). Myelination and Regional Domain Differentiation of the Axons. Results and Probl Cell Differ. In Cell Biology of Axon. Ed. Koenig, N.Y.
Pillai, A.M., Thaxton, C., Pribisko, A.L., Cheng, J.G., Dupree, J.L., Bhat, M.A. (2009) Spatiotemporal ablation of myelinating glia-specific neurofascin (Nfasc(NF155)) in mice reveals gradual loss of axoglial junctions and concomitant disorganization of axonal domains. J Neurosci Res 87 (8): 1773-93.
Thaxton, C., Lopera, J., Bott, M., Fernandez-Valle, C. (2008). Neuregulin and laminin stimulate phosphorylation of the NF2 tumor suppressor in Schwann cells by distinct protein kinase A and p21-activated kinase dependent pathways. Oncogene 27(19): 2705-15.
Thaxton, C., Lopera, J., Bott, M., Baldwin, M.E., Kalidas, P., Fernandez-Valle, C. (2007) Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated cy Cdc42-Pak and requires paxillin binding. Mol Cell Neurosci 34(2): 231-42.