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Publication : Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites.

First Author  Liu C Year  2018
Journal  Cell Volume  172
Issue  4 Pages  706-718.e15
PubMed ID  29398114 Mgi Jnum  J:268178
Mgi Id  MGI:6269133 Doi  10.1016/j.cell.2018.01.008
Citation  Liu C, et al. (2018) Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites. Cell 172(4):706-718.e15
abstractText  Dopamine controls essential brain functions through volume transmission. Different from fast synaptic transmission, where neurotransmitter release and receptor activation are tightly coupled by an active zone, dopamine transmission is widespread and may not necessitate these organized release sites. Here, we determine whether striatal dopamine secretion employs specialized machinery for release. Using super resolution microscopy, we identified co-clustering of the active zone scaffolding proteins bassoon, RIM and ELKS in approximately 30% of dopamine varicosities. Conditional RIM knockout disrupted this scaffold and, unexpectedly, abolished dopamine release, while ELKS knockout had no effect. Optogenetic experiments revealed that dopamine release was fast and had a high release probability, indicating the presence of protein scaffolds for coupling Ca(2+) influx to vesicle fusion. Hence, dopamine secretion is mediated by sparse, mechanistically specialized active zone-like release sites. This architecture supports spatially and temporally precise coding for dopamine and provides molecular machinery for regulation.
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