EFFECTS OF CALCIUM-BINDING PROTEINS (S-100A(O), S-100A, S-100B) ON DESMIN ASSEMBLY IN-VITRO

S-100a(o), the alpha alpha isoform of a subfamily of Ca2+-binding prot eins of the EF-hand type expressed in cardiac and skeletal muscle cell s, is reported to inhibit the assembly of the intermediate filament su bunit desmin and to stimulate the disassembly of desmin intermediate f ilaments in the presence of micromolar levels of free Ca2+, These effe cts are dose-dependent with respect to the S-100a(o) concentration and maximal at a desmin/S-100a(o) (dimer) molar ratio of similar to 2, Ot her members of the S-100 subfamily [S-100a (alpha beta) and S-100b (be ta beta)] and the unfractionated mixture of S-100a plus S-100b produce qualitatively similar effects on desmin assembly, with a potency that depends on the fraction of S-100 alpha subunit (the most potent) or S -100 beta subunit (the least potent) present in the S-100 isoforms tes ted, A binding stoichiometry of 2 mol of desmin/mol of S-100a(o) (dime r) and an affinity in the submicromolar range are calculated, The S-10 0 beta subunit also interacts with desmin, but with a lower affinity c ompared with S-100 alpha. By contrast, the S-100-like proteins calcycl in and p11 neither interact with desmin nor affect desmin assembly, Th e present data suggest that S-100a(o) might play a role in the regulat ion of the state of assembly of desmin intermediate filaments.