| First Author | Houy S | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 29274147 | Mgi Jnum | J:254968 |
| Mgi Id | MGI:6110885 | Doi | 10.7554/eLife.27000 |
| Citation | Houy S, et al. (2017) Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs. Elife 6:e27000 |
| abstractText | Doc2B is a cytosolic protein with binding sites for Munc13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca(2+) and SNAREs. Whether Doc2B functions as a calcium sensor akin to synaptotagmins, or in other calcium-independent or calcium-dependent capacities is debated. We here show by mutation and overexpression that Doc2B plays distinct roles in two sequential priming steps in mouse adrenal chromaffin cells. Mutating Ca(2+)-coordinating aspartates in the C2A-domain localizes Doc2B permanently at the plasma membrane, and renders an upstream priming step Ca(2+)-independent, whereas a separate function in downstream priming depends on SNARE-binding, Ca(2+)-binding to the C2B-domain of Doc2B, interaction with ubMunc13-2 and the presence of synaptotagmin-1. Another function of Doc2B - inhibition of release during sustained calcium elevations - depends on an overlapping protein domain (the MID-domain), but is separate from its Ca(2+)-dependent priming function. We conclude that Doc2B acts as a vesicle priming protein. |
