title: A Synaptotagmin Isoform Switch during the Development of an Identified CNS Synapse.
abstract: Various Synaptotagmin (Syt) isoform genes are found in mammals, but it is unknown whether Syts can function redundantly in a given nerve terminal, or whether isoforms can be switched during the development of a nerve terminal. Here, we investigated the possibility of a developmental Syt isoform switch using the calyx of Held as a model synapse. At mature calyx synapses, fast Ca(2+)-driven transmitter release depended entirely on Syt2, but the release phenotype of Syt2 knockout (KO) mice was weaker at immature calyces, and absent at pre-calyceal synapses early postnatally. Instead, conditional genetic inactivation shows that Syt1 mediates fast release at pre-calyceal synapses, as well as a fast release component resistant to Syt2 deletion in immature calyces. This demonstrates a developmental Syt1-Syt2 isoform switch at an identified synapse, a mechanism that could fine-tune the speed, reliability, and plasticity of transmitter release at fast releasing CNS synapses.
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain-Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: olexiy.kochubey@epfl.ch.
authors.forename: Olexiy
authors.initials: O
authors.lastname: Kochubey
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain-Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Institute of Animal Physiology & Department of Biology, Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Babai
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain-Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: ralf.schneggenburger@epfl.ch.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism*; D050861:Synaptotagmin II / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D050863:Synaptotagmin I; D050861:Synaptotagmin II; C494311:Syt1 protein, mouse; C494263:Syt2 protein, mouse