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Publication : Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release.

First Author  Yao J Year  2011
Journal  Cell Volume  147
Issue  3 Pages  666-77
PubMed ID  22036572 Mgi Jnum  J:178686
Mgi Id  MGI:5299947 Doi  10.1016/j.cell.2011.09.046
Citation  Yao J, et al. (2011) Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. Cell 147(3):666-77
abstractText  Synaptic transmission involves a fast synchronous phase and a slower asynchronous phase of neurotransmitter release that are regulated by distinct Ca(2+) sensors. Though the Ca(2+) sensor for rapid exocytosis, synaptotagmin I, has been studied in depth, the sensor for asynchronous release remains unknown. In a screen for neuronal Ca(2+) sensors that respond to changes in [Ca(2+)] with markedly slower kinetics than synaptotagmin I, we observed that Doc2--another Ca(2+), SNARE, and lipid-binding protein--operates on timescales consistent with asynchronous release. Moreover, up- and downregulation of Doc2 expression levels in hippocampal neurons increased or decreased, respectively, the slow phase of synaptic transmission. Synchronous release, when triggered by single action potentials, was unaffected by manipulation of Doc2 but was enhanced during repetitive stimulation in Doc2 knockdown neurons, potentially due to greater vesicle availability. In summary, we propose that Doc2 is a Ca(2+) sensor that is kinetically tuned to regulate asynchronous neurotransmitter release.
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