RT Journal Article SR Electronic T1 Synaptotagmin-7 Enhances Facilitation of Cav2.1 Calcium Channels JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0081-22.2022 DO 10.1523/ENEURO.0081-22.2022 VO 9 IS 3 A1 Djillani, Alaeddine A1 Bazinet, Jeremy A1 Catterall, William A. YR 2022 UL http://www.eneuro.org/content/9/3/ENEURO.0081-22.2022.abstract AB Voltage-gated calcium channel Cav2.1 undergoes Ca2+-dependent facilitation and inactivation, which are important in short-term synaptic plasticity. In presynaptic terminals, Cav2.1 forms large protein complexes that include synaptotagmins. Synaptotagmin-7 (Syt-7) is essential to mediate short-term synaptic plasticity in many synapses. Here, based on evidence that Cav2.1 and Syt-7 are both required for short-term synaptic facilitation, we investigated the direct interaction of Syt-7 with Cav2.1 and probed its regulation of Cav2.1 function. We found that Syt-7 binds specifically to the α1A subunit of Cav2.1 through interaction with the synaptic-protein interaction (synprint) site. Surprisingly, this interaction enhances facilitation in paired-pulse protocols and accelerates the onset of facilitation. Syt-7α induces a depolarizing shift in the voltage dependence of activation of Cav2.1 and slows Ca2+-dependent inactivation, whereas Syt-7β and Syt-7γ have smaller effects. Our results identify an unexpected, isoform-specific interaction between Cav2.1 and Syt-7 through the synprint site, which enhances Cav2.1 facilitation and modulates its inactivation.