Loss of AP-3 function affects spontaneous and evoked release at hippocampal mossy fiber synapses.
Synaptic vesicle (SV) exocytosis mediating neurotransmitter release occurs spontaneously at low intraterminal calcium concentrations and is stimulated by a rise in intracellular calcium. Exocytosis is compensated for by the reformation of vesicles at plasma membrane and endosomes. Although the adaptor complex AP-3 was proposed to be involved in the formation of SVs from endosomes, whether its function has an indirect effect on exocytosis remains unknown. Using mocha mice, which are deficient in functional AP-3, we identify an AP-3-dependent tetanus neurotoxin-resistant asynchronous release that can be evoked at hippocampal mossy fiber (MF) synapses. Presynaptic targeting of the tetanus neurotoxin-resistant vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is lost in mocha hippocampal MF terminals, whereas the localization of synaptobrevin 2 is unaffected. In addition, quantal release in mocha cultures is more frequent and more sensitive to sucrose. We conclude that lack of AP-3 results in more constitutive secretion and loss of an asynchronous evoked release component, suggesting an important function of AP-3 in regulating SV exocytosis at MF terminals.
Scheuber
Anita
A
Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche 739, Cortex and Epilepsy, F-75013 Paris, France.
Rudge
Rachel
R
Danglot
Lydia
L
Raposo
Graca
G
Binz
Thomas
T
Poncer
Jean-Christophe
JC
Galli
Thierry
T
D033963:Adaptor Protein Complex 3; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D009997:Osmotic Pressure; D012680:Sensitivity and Specificity; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D033963:Adaptor Protein Complex 3; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D020126:Brefeldin A; D002118:Calcium