| First Author | Coultrap SJ | Year | 2014 |
| Journal | Cell Rep | Volume | 6 |
| Issue | 3 | Pages | 431-7 |
| PubMed ID | 24485660 | Mgi Jnum | J:208776 |
| Mgi Id | MGI:5565023 | Doi | 10.1016/j.celrep.2014.01.005 |
| Citation | Coultrap SJ, et al. (2014) Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection. Cell Rep 6(3):431-7 |
| abstractText | Traditionally, hippocampal long-term potentiation (LTP) of synaptic strength requires Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) and other kinases, whereas long-term depression (LTD) requires phosphatases. Here, we found that LTD also requires CaMKII and its phospho-T286-induced "autonomous" (Ca(2+)-independent) activity. However, whereas LTP is known to induce phosphorylation of the AMPA-type glutamate receptor (AMPAR) subunit GluA1 at S831, LTD instead induced CaMKII-mediated phosphorylation at S567, a site known to reduce synaptic GluA1 localization. GluA1 S831 phosphorylation by "autonomous" CaMKII was further stimulated by Ca(2+)/CaM, as expected for traditional substrates. By contrast, GluA1 S567 represents a distinct substrate class that is unaffected by such stimulation. This differential regulation caused GluA1 S831 to be favored by LTP-type stimuli (strong but brief), whereas GluA1 S567 was favored by LTD-type stimuli (weak but prolonged). Thus, requirement of autonomous CaMKII in opposing forms of plasticity involves distinct substrate classes that are differentially regulated to enable stimulus-dependent substrate-site preference. |
