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Neurofilaments (NFs) are the most abundant cytoskeletal filaments undergoing 'slow axonal transport' in axons, and the population of NFs determines the axonal morphology. Both in vitro and ex-vivo experimental evidences show that the caliber of node is much thinner and the number of NFs in the node is much lower than the internode. Based on the Continuity equation, lower population of NFs indicates faster transport velocity. We propose that the local acceleration of NFs transport at node may result from the higher on-track rate [Formula: see text] or higher transition rate [Formula: see text] from pausing to running. We construct a segment of axon including both node and internode, and inject NFs by a fixed flux into it continuously. By upregulating transition rate of either [Formula: see text] or [Formula: see text] locally at the Node of Ranvier in the '6-state'model, we successfully accelerate NFs velocity and reproduce constriction of nodes. Our work demonstrates that local modulation of NF kinetics can change NFs distribution and shape the morphology of Node of Ranvier.

Neurofilaments(NFs) are the most abundant intermediate filaments that make up the inner volume of axon, with possible phosphorylation on their side arms, and their slow axonal transport by molecular motors along microtubule tracks in a "stop-and-go" manner with rapid, intermittent and bidirectional motion. The kinetics of NFs and morphology of axon are dramatically different between myelinate internode and unmyelinated node of Ranvier. The NFs in the node transport as 7.6 times faster as in the internode, and the distribution of NFs population in the internode is 7.6 folds as much as in the node of Ranvier. We hypothesize that the phosphorylation of NFs could reduce the on-track rate and slow down their transport velocity in the internode. By modifying the '6-state' model with (a) an extra phosphorylation kinetics to each six state and (b) construction a new '8-state' model in which NFs at off-track can be phosphorylated and have smaller on-track rate, our model and simulation demonstrate that the phosphorylation-induced decrease of on-track rate could slow down the NFs average velocity and increase the axonal caliber. The degree of phosphorylation may indicate the extent of velocity reduction. The Continuity equation used in our paper predicts that the ratio of NFs population is inverse proportional to the ratios of average velocity of NFs between node of Ranvier and internode. We speculate that the myelination of axon could increase the level of phosphorylation of NF side arms, and decrease the possibility of NFs to get on-track of microtubules, therefore slow down their transport velocity. In summary, our work provides a potential mechanism for understanding the phosphorylation kinetics of NFs in regulating their transport and morphology of axon in myelinated axons, and the different kinetics of NFs between node and internode. [ABSTRACT FROM AUTHOR]