  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.
