Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75(NTR)

Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor neurons based on a fluorescent fragment of tetanus toxin (TeNT H(C)). Morphological and kinetic analysis of TeNT H(C) retrograde carriers reveals two major groups of organelles: round vesicles and fast tubular structures. TeNT H(C) carriers lack markers of the classical endocytic pathway and are not acidified during axonal transport. Importantly, TeNT H(C) and NGF share the same retrograde transport organelles, which are characterized by the presence of the neurotrophin receptor p75(NTR). Our results provide the first direct visualization of retrograde transport in living motor neurons, and reveal a novel retrograde route that could be used both by physiological ligands (i.e., neurotrophins) and TeNT to enter the central nervous system.