| First Author | Moro A | Year | 2020 |
| Journal | PLoS Biol | Volume | 18 |
| Issue | 8 | Pages | e3000826 |
| PubMed ID | 32776935 | Mgi Jnum | J:294735 |
| Mgi Id | MGI:6453725 | Doi | 10.1371/journal.pbio.3000826 |
| Citation | Moro A, et al. (2020) CaMKII controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles. PLoS Biol 18(8):e3000826 |
| abstractText | Ca2+/calmodulin-dependent kinase II (CaMKII) regulates synaptic plasticity in multiple ways, supposedly including the secretion of neuromodulators like brain-derived neurotrophic factor (BDNF). Here, we show that neuromodulator secretion is indeed reduced in mouse alpha- and betaCaMKII-deficient (alphabetaCaMKII double-knockout [DKO]) hippocampal neurons. However, this was not due to reduced secretion efficiency or neuromodulator vesicle transport but to 40% reduced neuromodulator levels at synapses and 50% reduced delivery of new neuromodulator vesicles to axons. alphabetaCaMKII depletion drastically reduced neuromodulator expression. Blocking BDNF secretion or BDNF scavenging in wild-type neurons produced a similar reduction. Reduced neuromodulator expression in alphabetaCaMKII DKO neurons was restored by active betaCaMKII but not inactive betaCaMKII or alphaCaMKII, and by CaMKII downstream effectors that promote cAMP-response element binding protein (CREB) phosphorylation. These data indicate that CaMKII regulates neuromodulation in a feedback loop coupling neuromodulator secretion to betaCaMKII- and CREB-dependent neuromodulator expression and axonal targeting, but CaMKIIs are dispensable for the secretion process itself. |
