INTERACTION OF GANGLIOSIDE WITH SPECIFIC PEPTIDE SEQUENCES AS A MECHANISM FOR THE MODULATION OF CALMODULIN-DEPENDENT ENZYMES

We examined the interaction between gangliosides and synthetic peptide s of calmodulin (CaM)-dependent enzymes to confirm the hypothesis that interaction between gangliosides and the CaM-like site (CLS) of the e nzyme is a mechanism for the modulation of the enzyme activity by gang liosides. Gangliosides, GD1b, GT1b, and GD1a, inhibited the activity o f CaM-independently activated cAMP-phosphodiesterase and their inhibit ion was cancelled by a peptide consisting of 17 amino acid residues of a plasma membrane Ca2+-pump CLS, suggesting the involvement of the in teraction between the peptide and the gangliosides, The peptide of an assumed CLS of phosphodiesterase also cancelled the inhibition. On the other hand, the gangliosides interacted with synthetic CaM-binding si te (CBS) peptides of phosphodiesterase, calcineurin, Ca2+-pump, and Ca 2+/calmodulin-dependent protein kinase II. Moreover, gangliosides GM3 and LM1, that activate but do not inhibit phosphodiesterase, interacte d with the CBS peptides, whereas they did not bind to CLS peptides. On the basis of these new findings, we propose a revised model for the g anglioside-mediated modulation of CaM-dependent enzymes, i.e. without CaM, gangliosides bind to CBS and thus stimulate the enzyme activity, acting like CaM. AL higher concentrations, they bind to CLS of the enz ymes as well and inhibit the activity, acting like the CBS of the enzy me.