Local modulation of Neurofilament transport at Nodes of Ranvier

Abstract

Abstract 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 γ o n or higher transition rate γ 01 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 γ o n or γ 01 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.