Immunophilins are ubiquitous enzymes responsible for proline isomerisation 
during protein synthesis and for the chaperoning of several membrane proteins. 
These activities can be blocked by the immunosuppressants cyclosporin A, FK506 
and rapamycin. It has been shown that all three immunosuppressants have 
neurotrophic activity and can modulate neurotransmitter release, but the 
molecular basis of these effects is currently unknown. Here, we show that 
synapsin I, a synaptic vesicle-associated protein, can be purified from Torpedo 
cholinergic synaptosomes through its affinity to cyclophilin B, an immunophilin 
that is particularly abundant in brain. The interaction is direct and conserved 
in mammals, and shows a dissociation constant of about 0.5 microM in vitro. The 
binding between the two proteins can be disrupted by cyclosporin A and inhibited 
by physiological concentrations of ATP. Furthermore, cyclophilin B co-localizes 
with synapsin I in rat synaptic vesicle fractions and its levels in synaptic 
vesicle-containing fractions are decreased in synapsin knockout mice. These 
results suggest that immunophilins are involved in the complex protein networks 
operating at the presynaptic level and implicate the interaction between 
cyclophilin B and synapsins in presynaptic function.