title: Calmodulin stimulates the degradation of brain spectrin by calpain.
abstract: Brain spectrin has been shown to be a preferential substrate of calcium-dependent proteases (Baudry, Bundman, Smith, and Lynch: Science 212:937-938, 1981) and a major calmodulin-binding protein (Kakiuchi, Sobue, and Fujita: FEBS Lett. 132:144-148, 1981). Since calmodulin, spectrin, and a proteolytically derived spectrin fragment are all components of isolated postsynaptic density preparations (Grab, Berzins, Cohen, and Siekevitz: J. Biol. Chem. 254:8690-8696, 1979; Carlin, Bartelt, and Siekevitz: J. Cell Biol. 96:443-448, 1983), we investigated the functional role of calmodulin binding to brain spectrin with respect to its susceptibility to digestion by proteases. We report that calmodulin's interaction with brain spectrin results in a marked acceleration of the rate of spectrin degradation by calcium-dependent proteases (calpains I and II), but not by chymotrypsin. The cleavage of erythrocyte spectrin (which lacks a high-affinity calmodulin binding site) by calpain I is unaffected by the presence of calmodulin. The stimulatory effect of calmodulin is blocked by trifluoperazine, a calmodulin antagonist, which by itself does not modify brain spectrin proteolysis by calcium-dependent proteases. These results suggest a novel role for calmodulin in neuronal function--namely, a synergistic interaction with calcium-dependent proteases in the regulation of cytoskeletal integrity.
authors.affiliation: Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
authors.forename: P
authors.initials: P
authors.lastname: Seubert
authors.forename: M
authors.initials: M
authors.lastname: Baudry
authors.forename: S
authors.initials: S
authors.lastname: Dudek
authors.forename: G
authors.initials: G
authors.lastname: Lynch
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002147:Calmodulin / Q000494:pharmacology*; D002154:Calpain / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000201:enzymology; D007700:Kinetics; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D013049:Spectrin / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D013049:Spectrin; D010447:Peptide Hydrolases; D002154:Calpain