Van de Bospoort et al. describe how Munc13 proteins control when and where dense-core vesicles (DCVs) are released from neurons.
Neuronal DCVs contain neuropeptides and other factors that promote brain development and modulate synaptic transmission. Like neurotransmitter-containing synaptic vesicles (SVs), DCVs are released in response to action potentials and calcium influx, but relatively little is known about how neurons control DCV secretion. Van de Bospoort et al. designed a fluorescent probe to monitor the release of individual DCVs from hippocampal neurons in vitro.
Though DCVs weren’t enriched in synaptic terminals, they were preferentially secreted at synapses upon neuronal stimulation. DCV release from other parts of the neuron was less efficient and required prolonged stimulation. To investigate why DCVs are secreted more efficiently at synapses, Van de Bospoort et al. examined the Munc13 family of presynaptic proteins, which, by helping to assemble the SV fusion machinery, are essential for SV release.
DCVs were still secreted from neurons lacking Munc13 proteins, but their release required prolonged stimulation and no longer occurred preferentially at synapses. When Munc13-1 was overexpressed, on the other hand, it localized throughout neurons and boosted the efficiency of extrasynaptic DCV release, such that brief stimuli induced secretion equally from synaptic and nonsynaptic sites.
Therefore, although Munc13 proteins aren’t required for DCV exocytosis, they facilitate secretion at synaptic termini. The researchers now want to investigate how DCVs are recruited into synapses and to determine why DCV and SV secretion are regulated differently.
Text by Ben Short