| First Author | Bourgeois-Jaarsma Q | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 14408 |
| PubMed ID | 31594980 | Mgi Jnum | J:297992 |
| Mgi Id | MGI:6479487 | Doi | 10.1038/s41598-019-50684-1 |
| Citation | Bourgeois-Jaarsma Q, et al. (2019) Doc2b Ca(2+) binding site mutants enhance synaptic release at rest at the expense of sustained synaptic strength. Sci Rep 9(1):14408 |
| abstractText | Communication between neurons involves presynaptic neurotransmitter release which can be evoked by action potentials or occur spontaneously as a result of stochastic vesicle fusion. The Ca(2+)-binding double C2 proteins Doc2a and -b were implicated in spontaneous and asynchronous evoked release, but the mechanism remains unclear. Here, we compared wildtype Doc2b with two Ca(2+) binding site mutants named DN and 6A, previously classified as gain- and loss-of-function mutants. They carry the substitutions D218,220N or D163,218,220,303,357,359A respectively. We found that both mutants bound phospholipids at low Ca(2+) concentrations and were membrane-associated in resting neurons, thus mimicking a Ca(2+)-activated state. Their overexpression in hippocampal primary cultured neurons had similar effects on spontaneous and evoked release, inducing high mEPSC frequencies and increased short-term depression. Together, these data suggest that the DN and 6A mutants both act as gain-of-function mutants at resting conditions. |
