Despite the importance of dense core vesicle release in brain signalling, not much is known about the release mechanisms. To investigate how DCVs are released, van de Bospoort et al. designed a fluorescent probe to monitor the release of individual DCVs from hippocampal neurons in vitro.
Release notes for neuropeptide containing dense-core vesicles
Neuronal dense core vesicles transport and secrete neuropeptides that function in several brain processes, from axon guidance to tuning synaptic transmission. Despite the importance of dense core vesicle release in brain signalling, not much is known about dense core vesicle release mechanisms. To investigate how these vesicles are released, van de Bospoort et al. designed a fluorescent probe to monitor the release of individual DCVs from hippocampal neurons in vitro.
Her results are published in the December issue of The Journal of Cell Biology.
Van de Bospoort found that dense core vesicles preferentially fuse at synapses upon neuronal stimulation. DCV release from other additional parts of the neuron was less efficient and required more prolonged stimulation. Dense core vesicles were not enriched in synapses and often not pre-docked at the membrane suggesting that these vesicles are recruited to synaptic sites during activity.
To investigate why DCVs are secreted more efficiently at synapses, van de Bospoort et al. examined the Munc13 family of pre-synaptic proteins, which, by helping to assemble the SV fusion machinery, are essential for synaptic vesicle release. In neurons lacking Munc13, dense core vesicle release was severely hampered and release no longer occurred preferentially at synapses. Overexpression of Munc13, on the other hand, resulted in expression of Munc13 throughout the neuron and increased the release outside synaptic regions, suggesting that the presence of Munc13 is sufficient to create dense core vesicle release sites.
These results show that Munc13 proteins are important facilitators of neuronal dense core vesicle release at synaptic termini. Future studies lead by the Toonen and Verhage research groups will investigate how dense core vesicles are recruited into synapses before fusion.