CALCIUM-DEPENDENT ENDOGENOUS PROTEOLYSIS OF THE VESICLE PROTEINS SYNAPTOBREVIN AND SYNAPTOTAGMIN

THE synaptic vesicle integral protein synaptobrevin/VAMP is a target o f the clostridial metalloproteases tetanus toxin and botulinum toxins. We provide evidence that synaptobrevin can also be cleaved by an endo genous protease. As revealed by Western blotting proteolysis is calciu m-dependent, results in the formation of an 8 kD peptide that becomes apparent within 10 min. Proteolysis can be inhibited by the chelating agents EGTA and EDTA, whereas other protease inhibitors failed to prev ent degradation. In addition, a proteolytic degradation of the synapti c vesicle specific protein synaptotagmin could be observed. Other prot eins including the synaptic vesicle proteins synapsin I and synaptophy sin remained unaltered. Partial calcium-dependent degradation of selec t synaptic vesicle proteins may play a role in the life cycle of the o rganelle.