title: Presynaptic ryanodine receptor-activated calmodulin kinase II increases vesicle mobility and potentiates neuropeptide release.
abstract: Although it has been postulated that vesicle mobility is increased to enhance release of transmitters and neuropeptides, the mechanism responsible for increasing vesicle motion in nerve terminals and the effect of perturbing this mobilization on synaptic plasticity are unknown. Here, green fluorescent protein-tagged dense-core vesicles (DCVs) are imaged in Drosophila motor neuron terminals, where DCV mobility is increased for minutes after seconds of activity. Ca2+-induced Ca2+ release from presynaptic endoplasmic reticulum (ER) is shown to be necessary and sufficient for sustained DCV mobilization. However, this ryanodine receptor (RyR)-mediated effect is short-lived and only initiates signaling. Calmodulin kinase II (CaMKII), which is not activated directly by external Ca2+ influx, then acts as a downstream effector of released ER Ca2+. RyR and CaMKII are essential for post-tetanic potentiation of neuropeptide secretion. Therefore, the presynaptic signaling pathway for increasing DCV mobility is identified and shown to be required for synaptic plasticity.
authors.affiliation: Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Dinara
authors.initials: D
authors.lastname: Shakiryanova
authors.forename: Markus K
authors.initials: MK
authors.lastname: Klose
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tingting
authors.initials: T
authors.lastname: Gu
authors.forename: David L
authors.initials: DL
authors.lastname: Deitcher
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atwood
authors.forename: Randall S
authors.initials: RS
authors.lastname: Hewes
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Levitan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D007814:Larva; D009154:Mutation / Q000502:physiology; D009469:Neuromuscular Junction / Q000166:cytology*; D009479:Neuropeptides / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D049452:Green Fluorescent Proteins; D012433:Ryanodine; D000001:Calcimycin; D002110:Caffeine; C033170:4-bromo-A-23187; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium