Site-specific calcium-dependent proteolysis of neuronal protein GAP-43

GAP-43 is a presynaptic protein participating in signal transduction proces ses in nerve terminals. GAP-43 exists in neurons along with two truncated f orms devoid of 4 and 40 N-terminal residues. In this report. we show that t hese forms of GAP-43 are proteolytic fragments derived from calcium-depende nt cleavage of GAP-43 molecule at 5th and 41st residues. GAP-43 site-specif ic proteolysis in synaptosome and cytosol fractions proved to be dependent on the addition of millimolar amounts of calcium. This fact together with i nhibition of GAP-43 proteolysis by calpain inhibitors as well as local comp osition of the cleavage sites indicates to the participation of calpain in this process. The proteolysis disturbs some properties characteristic for w hole GAP-43 molecules, in particular, calmodulin binding and Ser-41 phospho rylation, when the cleavage occurs at 41st residue. Some other GAP-43 prope rties (G(o) protein activation and membrane attachment) are retained by sep arate fragments. Therefore, calcium controlled site-specific proteolysis of GAP-43 can be of great physiological significance. (C) 3001 Elsevier Scien ce Ireland Ltd and the Japan Neuroscience Society. All rights reserved.