CAR-Associated Vesicular Transport of an Adenovirus in Motor Neuron Axons

PLoS Pathogens

Anne Keriel¹  Daniel Henaff²  Giampietro Schiavo²  Sara Salinas³  Lynsey G. Bilsland³  Anne E. Weston⁴  Eric J. Kremer⁴ 

[1] Electron Microscopy Laboratory, Cancer Research UK London Research Institute, London, United Kingdom;Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Montpellier, France;Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom;Universités de Montpellier I & II, Montpellier, France

关键词: Axonal transport;    Virions;    Axons;    Adenoviruses;    Cellular structures;    organelles;    Endosomes;    Neurons;    Dyneins;   

DOI  :  10.1371/journal.ppat.1000442

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY