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CAR-associated vesicular transport of an adenovirus in motor neuron axons.

Salinas, S; Bilsland, LG; Henaff, D; Weston, AE; Keriel, A; Schiavo, G; Kremer, EJ; (2009) CAR-associated vesicular transport of an adenovirus in motor neuron axons. PLoS Pathog , 5 (5) , Article e1000442. 10.1371/journal.ppat.1000442. Green open access

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Abstract

Axonal transport is responsible for the movement of signals and cargo between nerve termini and cell bodies. Pathogens also exploit this pathway to enter and exit the central nervous system. In this study, we characterised the binding, endocytosis and axonal transport of an adenovirus (CAV-2) that preferentially infects neurons. Using biochemical, cell biology, genetic, ultrastructural and live-cell imaging approaches, we show that interaction with the neuronal membrane correlates with coxsackievirus and adenovirus receptor (CAR) surface expression, followed by endocytosis involving clathrin. In axons, long-range CAV-2 motility was bidirectional with a bias for retrograde transport in nonacidic Rab7-positive organelles. Unexpectedly, we found that CAR was associated with CAV-2 vesicles that also transported cargo as functionally distinct as tetanus toxin, neurotrophins, and their receptors. These results suggest that a single axonal transport carrier is capable of transporting functionally distinct cargoes that target different membrane compartments in the soma. We propose that CAV-2 transport is dictated by an innate trafficking of CAR, suggesting an unsuspected function for this adhesion protein during neuronal homeostasis.

Type: Article
Title: CAR-associated vesicular transport of an adenovirus in motor neuron axons.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1000442
Publisher version: http://dx.doi.org/10.1371/journal.ppat.1000442
Language: English
Additional information: Copyright: © 2009 Salinas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Cancer Research UK (GS and SS), the Motor Neurone Disease Association and the Jean Coubrough Charitable Trust (LB), the Association Française contre les Myopathies (EJK), Vaincre les Maladies Lysosomales (EJK), the Region Languedoc Roussilon (EJK) and BrainCAV, an EC-FP7 project (FP7-222992). EJK, SS and AK are Inserm fellows. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Adenoviridae, Animals, Axonal Transport, Axons, Carbocyanines, Cells, Cultured, Clathrin-Coated Vesicles, Coated Pits, Cell-Membrane, Endocytosis, Endosomes, Fluorescent Dyes, Ganglia, Spinal, Hydrogen-Ion Concentration, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Motor Neurons, Nerve Tissue Proteins, Rats, Receptors, Cytoplasmic and Nuclear, Sciatic Nerve, Transcription Factors, Vesicular Transport Proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1318634
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