Retrograde axonal transport of neurotrophins: differences between neuronal populations and implications for motor neuron disease.

During development, neurons die if they do not receive neurotrophin support from the target cells they are innervating. Neurotrophins are delivered from the target to the cell bodies of the innervating neurons by interacting with specific receptors located on the nerve terminals and then together are retrogradely transported to the cell body. This process consists of a number of distinct events including endocytosis of neurotrophin and its receptor into coated vesicles; vesicle sorting followed by retrograde axonal transport to the cell body, where interaction of the activated receptor initiates a signalling cascade at the cell body that causes the survival response. It has recently been shown that the signalling molecules associated with retrograde transport differ between neuronal populations. In sympathetic but not sensory neurons, a wortmannin-sensitive molecule (phosphatidylinositol kinase) is essential for the retrograde transport of neurotrophins. In sensory but not sympathetic neurons, a rapamycin-sensitive molecule (pp70S6K) is associated with retrograde transport of neurotrophins. This is strong evidence that sympathetic and sensory neurons utilize different signalling pathways to perform the same cellular function; retrograde transport. These findings may provide clues to understanding neurological diseases, such as motor neuron disease, in which axonal transport is impaired specifically in motor neurons.