Molecular and functional architecture of striatal dopamine release sites

• DOI: 10.1016/j.neuron.2021.10.028
• Publication Date: 2021-11-11T15:29:54Z
• Authors: Aditi Banerjee; Cordelia Imig; Karthik Balakrishnan; Lauren Kershberg; Noa Lipstein; Riikka-Liisa Uronen; Jiexin Wang; Xintong Cai; Fritz Benseler; Jeong Seop Rhee; Benjamin H. Cooper; Changliang Liu; Sonja M. Wojcik; Nils Brose; Pascal S. Kaeser
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Dopamine; Synapses; Synaptic Transmission; Corpus Striatum; Exocytosis

AbstractDopamine controls striatal circuit function, but its transmission mechanisms are not well understood. We recently showed that dopamine secretion requires RIM, suggesting that it occurs at active zone-like sites similar to conventional synapses. Here, we establish using a systematic conditional gene knockout approach that Munc13 and Liprin-α, active zone proteins for vesicle priming and release site organization, are important for dopamine secretion. Correspondingly, RIM zinc finger and C2B domains, which bind to Munc13 and Liprin-α, respectively, are needed to restore dopamine release in RIM knockout mice. In contrast, and different from conventional synapses, the active zone scaffolds RIM-BP and ELKS, and the RIM domains that bind to them, are expendable. Hence, dopamine release necessitates priming and release site scaffolding by RIM, Munc13, and Liprin-α, but other active zone proteins are dispensable. Our work establishes that molecularly simple but efficient release site architecture mediates fast dopamine exocytosis.