Excitatory amino acids activate calpain I and induce structural protein breakdown in vivo.
Neuronal activity regulates the catabolism of specific structural proteins in adult mammalian brain. Pharmacological stimulation of rat hippocampal neurons by systemic or intraventricular administration of the excitatory amino acids kainate or N-methyl-D-aspartate induces selective loss of brain spectrin and the microtubule-associated protein MAP2, as determined by quantitative immunoblotting, but not of actin, the high molecular weight neurofilament polypeptide, or glial fibrillary acidic protein. The spectrin decrease occurs primarily by enhanced proteolysis, as levels of the major breakdown products of the alpha-subunit increase more than 7-fold. This proteolysis may occur from activation of the calcium-dependent neutral protease calpain I. The immunopeptide maps produced by alpha-spectrin degradation, selective loss of spectrin and MAP2, and decrease in calpain I levels are all consistent with calpain I activation accompanied by autoproteolysis. We propose that calcium influx and calpain I activation provide a mechanism by which neuronal activity regulates the degradation of specific neuronal structural proteins and may thereby modify neuronal morphology.
Siman
R
R
Neuroscience Group, DuPont Company, Wilmington, Delaware 19898.
Noszek
J C
JC
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002154:Calpain / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010449:Peptide Mapping; D051381:Rats; D011919:Rats, Inbred Strains; D013049:Spectrin / Q000378:metabolism; D013379:Substrate Specificity
D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D013049:Spectrin; D001224:Aspartic Acid; D016202:N-Methylaspartate; D002154:Calpain; D007608:Kainic Acid