CaMKII controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles.
Animals
Astrocytes
/ cytology
Brain-Derived Neurotrophic Factor
/ genetics
Calcium
/ metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
/ deficiency
Cyclic AMP Response Element-Binding Protein
/ genetics
Feedback, Physiological
Gene Expression Regulation
Hippocampus
/ cytology
Mice
Mice, Transgenic
Neurons
/ cytology
Phosphorylation
Primary Cell Culture
Protein Subunits
/ deficiency
Synapses
/ physiology
Synaptic Transmission
Time-Lapse Imaging
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
27
09
2019
accepted:
17
07
2020
revised:
25
08
2020
pubmed:
11
8
2020
medline:
18
9
2020
entrez:
11
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32776935
doi: 10.1371/journal.pbio.3000826
pii: PBIOLOGY-D-19-02844
pmc: PMC7447270
doi:
Substances chimiques
Bdnf protein, mouse
0
Brain-Derived Neurotrophic Factor
0
Creb1 protein, mouse
0
Cyclic AMP Response Element-Binding Protein
0
Protein Subunits
0
Calcium-Calmodulin-Dependent Protein Kinase Type 2
EC 2.7.11.17
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000826Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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