Calcium-dependent endogenous proteolysis of the vesicle proteins synaptobrevin and synaptotagmin

The synaptic vesicle integral protein synaptobrevin/VAMP is a target of the clostridial metalloproteases tetanus toxin and botulinum toxins. We provide evidence that synaptobrevin can also be cleaved by an endogenous protease. As revealed by Western blotting proteolysis is calcium-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 prevent degradation. In addition, a proteolytic degradation of the synaptic vesicle specific protein synaptotagmin could be observed. Other proteins including the synaptic vesicle proteins synapsin I and synaptophysin remained unaltered. Partial calcium-dependent degradation of select synaptic vesicle proteins may play a role in the life cycle of the organelle.