Synapsin associates with cyclophilin B in an ATP- and cyclosporin A-dependent manner.
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.
Lane-Guermonprez
Lydie
L
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR 9040, Gif sur Yvette Cedex, France.
Morot-Gaudry-Talarmain
Yvette
Y
Meunier
François-Marie
FM
O'Regan
Seana
S
Onofri
Franco
F
Le Caer
Jean-Pierre
JP
Benfenati
Fabio
F
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D021983:Cyclophilins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000187:drug effects / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016704:Synapsins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014101:Torpedo
D007166:Immunosuppressive Agents; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D016704:Synapsins; C081786:cyclophilin B; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D019703:Calcineurin; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase