In order to rapidly relay signals through the conduction of action potentials, neuronal axons must have a substantial diameter. During axon radial growth, which is regulated by myelinating oligodendroglia, neurofilaments accumulate within the expanding region in a process that is not well understood. Researchers at HMS now contribute new information that identifies a particular phosphorylation event as crucial to this accumulation. The work is published in the Nov. 27 Journal of Cell Biology. Past research has suggested that either interneurofilament spacing or subunit composition might account for the accumulation of neurofilaments and the radial expansion of axons.
Subunits consist of heavy, medium, and light neuronal intermediate filaments.
Using several mouse models, Ralph Nixon , former HMS associate professor of psychiatry and currently at New York University School of Medicine, and his colleagues found that subunits assemble within an axon much earlier than the occurrence of radial expansion. In fact, mice with defects in myelination were deficient in the KSP phosphorylation of neurofilaments. And neurons deficient in heavy subunits maintained their axonal diameter by compensating for the critical KSP epitope on medium neurofilament subunits. The group found that this particular phosphorylation event is the only change that coincides with axon expansion during myelination and occurs selectively within regions of the axon that undergo neurofilament accumulation. In order to establish the diversity of the immune system, immunoglobulin and T cell receptor genes undergo a complex series of recombinatory steps necessary for the expression of the correct receptors in the appropriate cells.