The node of Ranvier influences the in vivo axonal transport of mitochondria and signaling endosomes
Andrew P. Tosolini,
Federico Abatecola,
Samuele Negro,
James N. Sleigh,
Giampietro Schiavo
Affiliations
Andrew P. Tosolini
Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, QLD 4067, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4067, Australia; Corresponding author
Federico Abatecola
Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
Samuele Negro
Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy; U.O.C. Clinica Neurologica, Azienda Ospedale, University of Padua, 35128 Padua, Italy
James N. Sleigh
Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1E 6BT, UK
Giampietro Schiavo
Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1E 6BT, UK; Corresponding author
Summary: Efficient long-range axonal transport is essential for maintaining neuronal function, and perturbations in this process underlie severe neurological diseases. Nodes of Ranvier (NoR) are short, specialized unmyelinated axonal domains with a unique molecular and structural composition. Currently, it remains unresolved how the distinct molecular structures of the NoR impact axonal transport dynamics. Using intravital time-lapse microscopy of sciatic nerves in live, anesthetized mice, we reveal (1) similar morphologies of the NoR in fast and slow motor axons, (2) signaling endosomes and mitochondria accumulate specifically at the distal node, and (3) unique axonal transport profiles of signaling endosomes and mitochondria transiting through the NoR. Collectively, these findings provide important insights into the fundamental physiology of peripheral nerve axons, motor neuron subtypes, and diverse organelle dynamics at the NoR. Furthermore, this work has relevance for several pathologies affecting peripheral nerves and the NoR.
