PHOSPHORYLATION MODULATES CALPAIN-MEDIATED PROTEOLYSIS AND CALMODULIN-BINDING OF THE 200-KDA AND 160-KDA NEUROFILAMENT PROTEINS

The effects of enzymatic dephosphorylation on neurofilament interactio n with two calcium-binding proteins, calpain and calmodulin, were exam ined. Dephosphorylation increased the rate and extent of 200-kDa neuro filament protein proteolysis by calpain. In contrast, dephosphorylatio n of the 160-kDa neurofilament protein did not alter the rate or exten t of calpain proteolysis. However, the calpain-induced breakdown produ cts of native and dephosphorylated 160-kDa neurofilament protein were different. Dephosphorylation did not change the proteolytic rate, exte nt, or breakdown products of the 68-kDa neurofilament protein. Calmodu lin binding to the purified individual 160- and 200-kDa neurofilament proteins was increased following dephosphorylation. These results sugg est that phosphorylation may regulate the metabolism and function of n eurofilaments by modulating interactions with the calcium-activated pr oteins calpain and calmodulin.