title: Dynamic control of synaptic vesicle replenishment and short-term plasticity by Ca(2+)-calmodulin-Munc13-1 signaling.
abstract: Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held, repetitive activity eventually results in short-term synaptic depression, which is in part due to the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by Ca(2+)-dependent vesicle replenishment, but the molecular mechanisms of this replenishment are largely unknown. We studied calyces of Held in knockin mice that express a Ca(2+)-Calmodulin insensitive Munc13-1(W464R) variant of the synaptic vesicle priming protein Munc13-1. Calyces of these mice exhibit a slower rate of synaptic vesicle replenishment, aberrant short-term depression and reduced recovery from synaptic depression after high-frequency stimulation. Our data establish Munc13-1 as a major presynaptic target of Ca(2+)-Calmodulin signaling and show that the Ca(2+)-Calmodulin-Munc13-1 complex is a pivotal component of the molecular machinery that determines short-term synaptic plasticity characteristics.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Noa
authors.initials: N
authors.lastname: Lipstein
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakaba
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Cooper
authors.forename: Kun-Han
authors.initials: KH
authors.lastname: Lin
authors.forename: Nicola
authors.initials: N
authors.lastname: Strenzke
authors.forename: Uri
authors.initials: U
authors.lastname: Ashery
authors.forename: Jeong-Seop
authors.initials: JS
authors.lastname: Rhee
authors.forename: Holger
authors.initials: H
authors.lastname: Taschenberger
authors.forename: Erwin
authors.initials: E
authors.lastname: Neher
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D009419:Nerve Tissue Proteins; C503321:Unc13a protein, mouse; D002118:Calcium