title: Posttranslational modification of nerve proteins by amino acids.
abstract: Both axonal and glial components of nerve are capable of carrying out reactions in which Arg, Lys, Leu, Pro, Val, AJa and Ser can be covalently linked to endogenous proteins in reactions which require tRNA but occur in the absence of ribosomes and ribosomal RNA. These posttranslational protein modifications appear to play important roles in nerve regeneration since they are increased more than 10-fold within 2 h of a crush injury in nerves which are capable of regeneration, but are not activated in nerves not capable of regrowth following injury. The regulation of the modification of proteins by Arg and Lys in vivo appears to be the function of separate peptides. The exogenous application of serine protease inhibitors (but not other protease inhibitors) mimics the effect of the endogenous peptides, suggesting that the endogenous regulators have serine protease inhibitory activity. The targets for modification are proteins of low abundance and thus far have been identified only in terms of their molecular weights and isoelectric points. The site of addition of Arg, but not the other amino acids, to target proteins is to the amino terminus. The addition of Arg to an amino terminus is likely to be involved in the ubiquitin mediated proteolysis of the modified protein. One of the most unusual findings in these series of experiments is that in regenerating sciatic nerves, amino acid modified proteins aggregate to form complexes of greater than 2 × 106 Da. The significance of this finding is not known. But we speculate that the aggregate may result from the assembly of an insoluble functional unit of the cell from soluble precursor proteins, and that the trigger for their assembly is amino acid modification.
authors.affiliation: Departments of Physiology and Neuroscience, UMD-New Jersey Medical School, Newark, NJ, 07103-2757 (U.S.A.).
authors.forename: N A
authors.initials: NA
authors.lastname: Ingoglia
authors.forename: G
authors.initials: G
authors.lastname: Chakraborty
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.forename: D
authors.initials: D
authors.lastname: Luo
authors.forename: C
authors.initials: C
authors.lastname: Liu