title: Enhanced level of site-specific proteolysis of GAP-43 protein during early stages of brain development.
abstract: GAP-43 protein of nerve terminals (B-50, F1, F57, pp46, neuromodulin) is thought to be one of key proteins involved in the control of outgrowth of neurites, release of neuromediators, synapse plasticity, etc. GAP-43 is usually 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 about forty N-terminal amino acid residues (GAP-43-2 and GAP-43-3, respectively). The full-length GAP-43 is predominant in the mature brain. However, the ratio of the full-length protein and its fragments can vary under different physiological conditions. Changes in the GAP-43 proteins (the full-length protein and its fragments) were studied during embryonal and postnatal development 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 increased, and, until the 10th day after birth, GAP-43-3 dominated rather than the 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 residues from the full-length GAP-43 molecule, is increased. The cleavage occurs in the region responsible for the interaction of GAP-43 with calmodulin. In the full-length molecule, this region is responsible also for the recognition of Ser41 residue by protein kinase C during phosphorylation. Another functionally important region that determines, in particular, the attachment 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 fragmentation of GAP-43 that depends on developmental stage should be considered as a controlled structural rearrangement fundamentally affecting the functions of this protein.
authors.affiliation: Petersburg Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Leningrad Region, 188350, Russia. mm5768@mm5768.spb.edu
authors.forename: M I
authors.initials: MI
authors.lastname: Mosevitsky
authors.forename: E S
authors.initials: ES
authors.lastname: Konovalova
authors.forename: N K
authors.initials: NK
authors.lastname: Bichevaya
authors.forename: B I
authors.initials: BI
authors.lastname: Klementiev
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D019922:GAP-43 Protein / Q000737:chemistry* / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism; D051381:Rats
chemical_list: D019922:GAP-43 Protein; D010450:Endopeptidases