| First Author | Sclip A | Year | 2018 |
| Journal | EMBO J | Volume | 37 |
| Issue | 16 | PubMed ID | 29967030 |
| Mgi Jnum | J:323964 | Mgi Id | MGI:7263320 |
| Doi | 10.15252/embj.201798637 | Citation | Sclip A, et al. (2018) RIM-binding proteins recruit BK-channels to presynaptic release sites adjacent to voltage-gated Ca(2+)-channels. EMBO J 37(16):e98637 |
| abstractText | The active zone of presynaptic nerve terminals organizes the neurotransmitter release machinery, thereby enabling fast Ca(2+)-triggered synaptic vesicle exocytosis. BK-channels are Ca(2+)-activated large-conductance K(+)-channels that require close proximity to Ca(2+)-channels for activation and control Ca(2+)-triggered neurotransmitter release by accelerating membrane repolarization during action potential firing. How BK-channels are recruited to presynaptic Ca(2+)-channels, however, is unknown. Here, we show that RBPs (for RIM-binding proteins), which are evolutionarily conserved active zone proteins containing SH3- and FN3-domains, directly bind to BK-channels. We find that RBPs interact with RIMs and Ca(2+)-channels via their SH3-domains, but to BK-channels via their FN3-domains. Deletion of RBPs in calyx of Held synapses decreased and decelerated presynaptic BK-currents and depleted BK-channels from active zones. Our data suggest that RBPs recruit BK-channels into a RIM-based macromolecular active zone complex that includes Ca(2+)-channels, synaptic vesicles, and the membrane fusion machinery, thereby enabling tight spatio-temporal coupling of Ca(2+)-influx to Ca(2+)-triggered neurotransmitter release in a presynaptic terminal. |
