TY - JOUR T1 - Synaptotagmin-7 Enhances Facilitation of Ca<sub>v</sub>2.1 Calcium Channels JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0081-22.2022 VL - 9 IS - 3 SP - ENEURO.0081-22.2022 AU - Alaeddine Djillani AU - Jeremy Bazinet AU - William A. Catterall Y1 - 2022/05/01 UR - http://www.eneuro.org/content/9/3/ENEURO.0081-22.2022.abstract N2 - 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. ER -