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 su pport from the target cells they are innervating. Neurotrophins are de livered 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 inter action of the activated receptor initiates a signalling cascade at the cell body that causes the survival response. It has recently been sho wn that the signalling molecules associated with retrograde transport differ between neuronal populations. In sympathetic but not sensory ne urons, a wortmannin-sensitive molecule (phosphatidylinositol kinase) i s essential for the retrograde transport of neurotrophins. In sensory but not sympathetic neurons, a rapamycin-sensitive molecule (pp70(S6K) ) is, associated with retrograde transport of neurotrophins. This is s trong 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 neurologi cal diseases, such as motor neuron disease, in which axonal transport is impaired specifically in motor neurons.