Cation-mediated release and proteolytic cleavage of basic protein of isolated human myelin at acid pH.

Myelin from human brain was incubated at pH 4.4 with metal salts, including KCl, NaCl, CaCl2, and MgSO4, to elicit cation-dependent autoproteolysis of myelin proteins. Incubation of myelin resulted in soluble proteolytic breakdown products of Mr smaller than those of the three original myelin basic proteins (MBPs). Comparable polypeptides were essentially absent from residual myelin. Proteolysis was strongly stimulated by increasing millimolar concentrations of K+, Na+, and Mg2+ and only moderately by Ca2+. Breakdown products were traced to MBP by immunostaining. Their origin from MBP was also indicated by identical electrophoretic cleavage patterns from endogenous myelin protein and exogenous MBP. All four metal salts, in addition to activating endogenous proteolysis, also caused a biphasic extraction of MBP. Electrophoresis of myelin revealed a quick initial and a slow further loss of protein, eventually leading to the removal of up to 78% of original MBP. The results are consistent with a concurrent extraction of MBP and activation of latent-bound acid protease activity by metal cations. It is therefore suggested that, in particular disease states, unfavorable changes in electrolytes and pH of white matter may cause a selective loss and proteolytic cleavage of MBP.