CaMKII controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles
PL o S Biology (Online) , Volume 18 - Issue 8 p. e3000826
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 α- and βCaMKII-deficient (αβCaMKII 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. αβCaMKII depletion drastically reduced neuromodulator expression. Blocking BDNF secretion or BDNF scavenging in wild-type neurons produced a similar reduction. Reduced neuromodulator expression in αβCaMKII DKO neurons was restored by active βCaMKII but not inactive βCaMKII or αCaMKII, 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 βCaMKII- and CREB-dependent neuromodulator expression and axonal targeting, but CaMKIIs are dispensable for the secretion process itself.
|PL o S Biology (Online)|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Moro, A. (Alessandro), van Woerden, G.M, Toonen, P.W, & Verhage, M. (2020). CaMKII controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles. PL o S Biology (Online), 18(8). doi:10.1371/journal.pbio.3000826