Target Regulation of Axotomy-Sensitive Proteins

Large changes in the production of certain proteins often follow axotomy. How the cell body is signaled to make these changes, or terminate them after regeneration is finished, is unclear. This issue was addressed by studying an axotomized giant identified neuron, the giant cerebral neuron of the sea slug Aplysia, both in vivo and in culture. One week after axon crush in vivo, there were increases of 1.5-18-fold in the 5-h incorporation of 35S]methionine into seven proteins identified by two-dimensional gel electrophoresis. There were decreases of five- to 28-fold in the labeling of four other proteins. An axotomized giant cerebral neuron grows vigorously when placed in culture and forms chemical synapses with appropriate target cells while continuing unabated growth. The labeling of two of the proteins that up-regulate after axotomy in vivo was suppressed by the presence of target cells in culture. For one of the proteins, this effect was also produced by membranes of target cells, but not by medium conditioned by exposure to target cells. These results are consistent with the idea that loss of membrane-membrane contact with target cells (or its restoration) is involved in the initiation (or termination) of the up-regulation of certain proteins after axotomy.