Review : The Synthesis, Axonal Transport, and Phosphorylation of Neurofilaments Determine Axonal Caliber in Myelinated Nerve Fibers

Abstract

Axonal diameter is the principal determinant of conduction velocity in myelinated nerve fibers, but, until recently, the factors that determine axonal diameter have not been understood. Recent studies indicate that neurofilaments (NFs), the principal intermediate (10-nm) filaments in neurons, are major intrinsic determinants of axonal caliber and have begun to elucidate the molecular mechanisms involved in NF deployment. The radial growth of myelinated axons during postnatal development reflects an increase in axonal NF content. The NF proteins are synthesized in the neuron cell body (soma) and transported somatofugally along axons in the slow component of axonal transport. The level of NF expression de termines the amount of NF protein transported in the slow component. In neurons with large axons, NF expression rises dramatically during neonatal development and is maintained at high steady-state levels as the NF content of axons increases during postnatal development. This increase in NF content, after NF expression has reached steady-state levels, appears to result from a progressive decline in the ve locity of NF transport, with increasing distance along nerve fibers (i.e., NFs enter a region of the axon faster than they leave). Phosphorylation of the NF proteins may regulate the spacing of axonal NFs and the velocity of NF transport. The Neuroscientist 1:76-83, 1995