title: Degradation of microtubule-associated protein 2 and brain spectrin by calpain: a comparative study.
abstract: The in vitro degradation of microtubule-associated protein 2 (MAP-2) and spectrin by the calcium-dependent neutral protease calpain was studied. Five major results are reported. First, MAP-2 isolated from twice-cycled microtubules (2 X MT MAP-2) was extremely sensitive to calpain-induced hydrolysis. Even at an enzyme-to-substrate ratio (wt/wt) of 1:200, 2 X MT MAP-2 was significantly degraded by calpain. Second, MAP-2 purified from the total brain heat-stable fraction (total MAP-2) was significantly more resistant to calpain-induced hydrolysis compared with 2 X MT MAP-2. Third, MAP-2a and MAP-2b were proteolyzed similarly by calpain, although some relative resistance of MAP-2b was observed. Fourth, the presence of calmodulin significantly increased the extent of calpain-induced hydrolysis of the alpha-subunit of spectrin. Fifth, the two neuronal isoforms of brain spectrin (240/235 and 240/235E, referred to as alpha/beta N and alpha/beta E, respectively) showed different sensitivities to calpain. alpha N-spectrin was significantly more sensitive to calpain-induced degradation compared to alpha E-spectrin. Among other things, these results suggest a role for the calpain-induced degradation of MAP-2, as well as spectrin, in such physiological processes as alterations in synaptic efficacy, dendritic remodeling, and in pathological processes associated with neurodegeneration.
authors.affiliation: Department of Neurology, University of Alabama, Birmingham.
authors.forename: G V
authors.initials: GV
authors.lastname: Johnson
authors.forename: J M
authors.initials: JM
authors.lastname: Litersky
authors.forename: R S
authors.initials: RS
authors.lastname: Jope
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism*; D006868:Hydrolysis; D007536:Isomerism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D008869:Microtubule-Associated Proteins; D013049:Spectrin; D002154:Calpain