Fioravante, DiasynouChu, Yunde Jong, Arthur PHLeitges, MichaelKaeser, PascalRegehr, Wade2014-09-082014Fioravante, Diasynou, YunXiang Chu, Arthur PH de Jong, Michael Leitges, Pascal S Kaeser, and Wade G Regehr. 2014. “Protein kinase C is a calcium sensor for presynaptic short-term plasticity.” eLife 3 (1): e03011. doi:10.7554/eLife.03011. http://dx.doi.org/10.7554/eLife.03011.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12785972In presynaptic boutons, calcium (Ca2+) triggers both neurotransmitter release and short-term synaptic plasticity. Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca2+ to their C2 domains, the proteins that sense smaller global Ca2+ increases to produce short-term plasticity have remained elusive. Here, we identify a Ca2+ sensor for post-tetanic potentiation (PTP), a form of plasticity thought to underlie short-term memory. We find that at the functionally mature calyx of Held synapse the Ca2+-dependent protein kinase C isoforms α and β are necessary for PTP, and the expression of PKCβ in PKCαβ double knockout mice rescues PTP. Disruption of Ca2+ binding to the PKCβ C2 domain specifically prevents PTP without impairing other PKCβ-dependent forms of synaptic enhancement. We conclude that different C2-domain-containing presynaptic proteins are engaged by different Ca2+ signals, and that Ca2+ increases evoked by tetanic stimulation are sensed by PKCβ to produce PTP. DOI: http://dx.doi.org/10.7554/eLife.03011.001en-USShort Reportpost-tetanic potentiationshort-term plasticityprotein kinase Csynaptotagminphorbol estercalciummouseJournal Article2014-09-0810.7554/eLife.03011