title: Synaptotagmin increases the dynamic range of synapses by driving Ca²+-evoked release and by clamping a near-linear remaining Ca²+ sensor.
abstract: Ca²+-evoked transmitter release shows a high dynamic range over spontaneous release. We investigated the role of the Ca²+ sensor protein, Synaptotagmin2 (Syt2), in both spontaneous and Ca²+-evoked release under direct control of presynaptic [Ca²+](i), using an in vivo rescue approach at the calyx of Held. Re-expression of Syt2 rescued the highly Ca²+ cooperative release and suppressed the elevated spontaneous release seen in Syt2 KO synapses. This latter release clamping function was partially mediated by the poly-lysine motif of the C₂B domain. Using an aspartate mutation in the C₂B domain (D364N) in which Ca²+ triggering was abolished but release clamping remained intact, we show that Syt2 strongly suppresses the action of another, near-linear Ca²+ sensor that mediates release over a wide range of [Ca²+](i). Thus, Syt2 increases the dynamic range of synapses by driving release with a high Ca²+ cooperativity, as well as by suppressing a remaining, near-linear Ca²+ sensor.
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Olexiy
authors.initials: O
authors.lastname: Kochubey
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001306:Auditory Pathways / Q000166:cytology / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D017626:Cochlear Nucleus / Q000166:cytology; D004558:Electric Stimulation / Q000379:methods; D007839:Functional Laterality / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050861:Synaptotagmin II / Q000172:deficiency / Q000378:metabolism*
chemical_list: D050861:Synaptotagmin II; C494263:Syt2 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001224:Aspartic Acid; D001216:Asparagine; D002118:Calcium