Regulation of Neuronal Protein Synthesis by Calcium

Neurons are an extreme example of a cell type whose architecture must have an influence on its local metabolism. Their extremely long projections, specially when axons are considered, together with ultrastructural characteristics such as the absence of concluding evidences for the presence of ribosomes inside axons, induced neurobiologists to propose different maintenance paradigms for the different parts of the neuron. Three neuronal territories will be discussed here, a) the axon; b) the soma and dendrites; and c) the synapse. The characteristics of the axonal territory will be described first. In accordance to the widespread dogma of the absence of ribosomes in axons, axonal proteins (structural ones or those functionally destinated to membranes or nerve endings) should be synthesized in the somatic territory and conveyed after towards the axon via two different velocity transport mechanisms [0.5 to 5 mm/day and 420 mm/day, respectively (for review see Ochs, 1982)]. The possibility that the axonal territory could synthesize some of its proteins has not been generally accepted. Thus, the half-life of each cytoskeletal axonal protein should be estimated to be several times longer than the duration of their transport to the nerve endings. For instance, if we consider neurofilament proteins (Nf)—which normally are transported at a rate of lmm/day—in a 1 meter length nerve, they will arrive to the nerve endings 1000 days after their synthesis. This could mean that if the half-life of Nf is 1000 days, 50% of the Nf transported to the nerve endings will be degraded before the original bulk arrives to its destination. Even with a half life of 4000 days (about 11 years), a 1/16 of the Nf transported to the nerve endings will not arrive given that they will be degraded. The above mentioned problem have been extensively discussed by Alvarez and Torrez (1985), whom proposed that under these conditions the most peripheral portions of axons should always be partially deprived of cytoskeletal proteins. Furthermore, it is well known from Cajal’s studies (1928) that the total volume of the axonal territory in the longest axons is more than three order of magnitude greater than the somatic territory. On the other hand, the branching of axons at their ends will increase instead of diminish their total volume, increasing even more their possible hindrance. However, axons have been generally found to be homogeneously healthy throughout their length (see Alvarez and Torrez, 1985). Consequently, a local system of protein synthesis should be considered to maintain the homogeneity of axons; otherwise, some special mechanisms for protecting axonal cytoskeletal proteins from degradation must be found in axons. Thus, whether the axonal territory may synthesize at least a part of its own proteins or not, should be a main question, the answer of which—if positive—would change the point of view of a lot of normal or pathological neuronal functions which are related to protein synthesis.