A protein associated with axon growth, GAP-43, is widely distributed and developmentally regulated in rat CNS.

Development or regeneration of axons in several systems is accompanied by 20-100-fold increases in the synthesis of an acidic, axonally transported membrane protein with an apparent molecular weight of 43-50,000 (Benowitz and Lewis, 1983; Skene and Willard, 1981a, b), which we designate GAP-43. We have proposed that some step(s) in axon growth require production of GAP-43, and perhaps a small number of other "growth-associated proteins," at rates much higher than those typical of mature neurons. This hypothesis predicts that virtually all neurons synthesize GAP-43 at elevated levels during normal CNS development. Here we show that a protein similar to GAP-43 from regenerating toad nerves is prominent among the newly synthesized (35S-methionine-labeled) and total (Coomassie blue-stained) proteins in neonatal rat cerebral cortex and cerebellum, suggesting that synthesis of GAP-43 is indeed a common feature of many developing neurons. Synthesis and accumulation of the protein decline an order of magnitude as animals mature. Antibodies raised against the rat cortex GAP-43 also recognize electrophoretically similar proteins from regenerating toad optic nerves and from developing hamster sensorimotor cortex, indicating that structural features of GAP-43 are conserved in evolution. Cell-free translation of polyadenylated RNA from neonatal and adult cortex suggests that developmental regulation of GAP-43 synthesis is mediated largely through changes in mRNA abundance. These observations together suggest that developmental regulation of GAP-43 gene expression may be common to most vertebrate CNS neurons. GAP-43 remains detectable at a low level in adult rat cortex, and it co-migrates on two-dimensional gels with B-50, a synaptic membrane protein which is a preferred substrate for protein kinase C in adult brains. Phosphorylation of the protein by endogenous kinase(s) in vitro is 4-7-fold greater in growth cone membranes than in mature synaptic membranes, which raises the possibility that local modification of the protein in axon terminals may be synergistic with regulation of GAP-43 synthesis in the cell body.