B-50, THE GROWTH-ASSOCIATED PROTEIN-43 - MODULATION OF CELL MORPHOLOGY AND COMMUNICATION IN THE NERVOUS-SYSTEM

The growth-associated protein B-50 (GAP-43) is a presynaptic protein. Its expression is largely restricted to the nervous system, B-50 is fr equently used as a marker for sprouting, because it is located in grow th cones, maximally expressed during nervous system development and re -induced in injured and regenerating neural tissues. The B-50 gene is highly conserved during evolution. The B-50 gene contains two promoter s and three exons which specify functional domains of the protein. The first exon encoding the 1-10 sequence, harbors the palmitoylation sit e for attachment to the axolemma and the minimal domain for interactio n with G(o) protein. The second exon contains the ''GAP module'', incl uding the calmodulin binding and the protein kinase C phosphorylation domain which is shared by the family of IQ proteins. Downstream sequen ces of the second and non-coding sequences in the third exon encode sp ecies variability. The third exon also contains a conserved domain for phosphorylation by casein kinase II. Functional interference experime nts using antisense oligonucleotides or antibodies, have shown inhibit ion of neurite outgrowth and neurotransmitter release. Overexpression of B-50 in cells or transgenic mice results in excessive sprouting. Th e various interactions, specified by the structural domains, are thoug ht to underlie the role of B-50 in synaptic plasticity, participating in membrane extension during neuritogenesis, in neurotransmitter relea se and long-term potentiation. Apparently, B-50 null-mutant mice do no t display gross phenotypic changes of the nervous system, although the B-50 deletion affects neuronal pathfinding and reduces postnatal surv ival. The experimental evidence suggests that neuronal morphology and communication are critically modulated by, but not absolutely dependen t Bon, (enhanced) B-50 presence. (C) 1997 Elsevier Science Ltd.