Degradation of Microtubule‐Associated Protein 2 and Brain Spectrin by Calpain: A Comparative Study

Gail V.W. Johnson, Joel M. Litersky, Richard S. Jope

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167 Scopus citations


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 (2XMT MAP-2) was extremely sensitive to calpain-induced hydrolysis. Even at an enzyme-to-substrate ratio (wt/ wt) of 1:200, 2XMT 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 2XMT 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 α-subunit of spectrin. Fifth, the two neuronal isoforms of brain spectrin (240/235 and 240/235E, referred to as α/βN and α/ βE, respectively) showed different sensitivities to calpain. αN-spectrin was significantly more sensitive to calpain-induced degradation compared to αE-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.

Original languageEnglish (US)
Pages (from-to)1630-1638
Number of pages9
JournalJournal of neurochemistry
Issue number5
StatePublished - May 1991
Externally publishedYes


  • Calpain
  • Microtubule-associated protein 2
  • Spectrin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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