Regulation of fast transported proteins in normal and regenerating frog retinal ganglion and dorsal root ganglion neurons

The most prominent fast transported proteins conveyed along the axons of retinal ganglion cells and dorsal root ganglion cells of the frog were studied, both in normal nerve and during nerve regeneration. Specific questions addressed were: (1) Do retinal ganglion cells and dorsal root ganglion cells express different fast transported proteins? (2) How do the patterns of fast transported proteins change after nerve damage, and do the amounts of these proteins transported in the axons change during nerve regeneration? (3) How does a neuron normally regulate its fast transported proteins and how is the regulation modified during regeneration? (4) Is there any damage-specific change in fast transported proteins which might serve as a signal for nerve regeneration, and how might it be produced?The most prominent fast transported proteins normally conveyed in the frog retinal ganglion cells and the dorsal root ganglion cells were analyzed in studies outlined in Chapter III. Analysis of the composition of fast transported proteins showed that there are two different sets of proteins that are unique to each type of neuron. The relative abundance of proteins commonly present in both neurons was also different, suggesting that neuronal cell bodies regulate not only the nature but also the amount of proteins rapidly transported along their axons.No new fast transported proteins were detected in the regenerating axons of either kind of neurons (Chapter IV). However, the total amounts of fast transported protein conveyed into the visual system had increased significantly. For each kind of neuron, several classes of changes in the relative abundance of fast transported proteins could be distinguished during the course of regeneration, suggesting that neurons can further regulate the amounts of fast transported proteins in order to meet the demand of the regenerating axons. The different classes of changes suggested various roles that these fast transported proteins might play in nerve regeneration.A protein (A25) that appeared specifically at the crush site of the frog optic and sciatic nerves, most likely by posttranslational modification, was further characterized in Chapter V. A25 had many characteristics that might be expected of a retrograde signal that activates the cell body response after nerve injury. The mechanism of how A25 might be produced was studied in experiments designed to block axonal transport by lowering the temperature of the nerve ( cold-block ). The results showed that A25 was produced proximal to a cold-block , indicating that physical damage, such as transection of the axon is not required for A25 production. The interaction between the precursor for A25 and the factor(s) responsible for its modification might have occurred when axonal transport was stopped by the cold-block , perhaps by mixing or fusion of transported vesicles