CAR-associated vesicular transport of an adenovirus in motor neuron axons.
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.
Salinas
Sara
S
Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
Bilsland
Lynsey G
LG
Henaff
Daniel
D
Weston
Anne E
AE
Keriel
Anne
A
Schiavo
Giampietro
G
Kremer
Eric J
EJ
D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000821:virology*; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000648:ultrastructure / Q000821:virology; D003034:Coated Pits, Cell-Membrane / Q000648:ultrastructure / Q000821:virology; D000090702:Constitutive Androstane Receptor; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D005456:Fluorescent Dyes / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
D002232:Carbocyanines; D000090702:Constitutive Androstane Receptor; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C089187:cyanine dye 3