Enhanced level of site-specific proteolysis of GAP-43 protein during earlystages of brain development

GAP-43 protein of nerve terminals (B-50, F1, F57, pp46, neuromodulin) is th ought to be one of key proteins involved in the control of outgrowth of neu rites, release of neuromediators, synapse plasticity, etc. GAP-43 is usuall y considered as a whole protein. Along with the intact protein, nerve cells also contain two large native fragments of GAP-43 deprived of four or of a bout forty N-terminal amino acid residues (GAP-43-2 and GAP-43-3, respectiv ely). The full-length GAP-43 is predominant in the mature brain. However, t he ratio of the full-length protein and its fragments can vary under differ ent physiological conditions. Changes in the GAP-43 proteins (the full-leng th protein and its fragments) were studied during embryonal and postnatal d evelopment of rat brain. The GAP-43 proteins were found to be expressed not later than on the 12-13th day of embryogenesis. Then their contents increa sed, and, until the 10th day after birth, GAP-43-3 dominated rather than th e full-length protein. It is suggested that during this period the activity of a specific protease, which cleaves the N-terminal peptide of about 40 r esidues from the full-length GAP-43 molecule, is increased. The cleavage oc curs in the region responsible for the interaction of GAP-43 with calmoduli n. In the full-length molecule, this region is responsible also for the rec ognition of Ser41 residue by protein kinase C during phosphorylation. Anoth er functionally important region that determines, in particular, the attach ment of GAP-43 to the plasma membrane is cleaved from the main part of the molecule together with the N-terminal peptide. Thus, the specific fragmenta tion of GAP-43 that depends on developmental stage should be considered as a controlled structural rearrangement fundamentally affecting the functions of this protein.