Activity-dependent liberation of synaptic neuropeptide vesicles.
Despite the importance of neuropeptide release, which is evoked by long bouts of action potential activity and which regulates behavior, peptidergic vesicle movement has not been examined in living nerve terminals. Previous in vitro studies have found that secretory vesicle motion at many sites of release is constitutive: Ca(2+) does not affect the movement of small synaptic vesicles in nerve terminals or the movement of large dense core vesicles in growth cones and endocrine cells. However, in vivo imaging of a neuropeptide, atrial natriuretic factor, tagged with green fluorescent protein in larval Drosophila melanogaster neuromuscular junctions shows that peptidergic vesicle behavior in nerve terminals is sensitive to activity-induced Ca(2+) influx. Specifically, peptidergic vesicles are immobile in resting synaptic boutons but become mobile after seconds of stimulation. Vesicle movement is undirected, occurs without the use of axonal transport motors or F-actin, and aids in the depletion of undocked neuropeptide vesicles. Peptidergic vesicle mobilization and post-tetanic potentiation of neuropeptide release are sustained for minutes.
Shakiryanova
Dinara
D
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Tully
Arvonn
A
Hewes
Randall S
RS
Deitcher
David L
DL
Levitan
Edwin S
ES
D000818:Animals; D030801:Animals, Genetically Modified; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004330:Drosophila; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D018613:Microscopy, Confocal / Q000379:methods; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D038761:Photobleaching; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013997:Time Factors
D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D002104:Cadmium; D049452:Green Fluorescent Proteins; D015638:Cytochalasin D; D009320:Atrial Natriuretic Factor; D005033:Ethylmaleimide; D002118:Calcium