Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.
Nat Commun
; 9(1): 2451, 2018 06 22.
Article
in En
| MEDLINE
| ID: mdl-29934532
ABSTRACT
Learning and memory depend on neuronal plasticity originating at the synapse and requiring nuclear gene expression to persist. However, how synapse-to-nucleus communication supports long-term plasticity and behavior has remained elusive. Among cytonuclear signaling proteins, γCaMKII stands out in its ability to rapidly shuttle Ca2+/CaM to the nucleus and thus activate CREB-dependent transcription. Here we show that elimination of γCaMKII prevents activity-dependent expression of key genes (BDNF, c-Fos, Arc), inhibits persistent synaptic strengthening, and impairs spatial memory in vivo. Deletion of γCaMKII in adult excitatory neurons exerts similar effects. A point mutation in γCaMKII, previously uncovered in a case of intellectual disability, selectively disrupts CaM sequestration and CaM shuttling. Remarkably, this mutation is sufficient to disrupt gene expression and spatial learning in vivo. Thus, this specific form of cytonuclear signaling plays a key role in learning and memory and contributes to neuropsychiatric disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calmodulin
/
Long-Term Potentiation
/
Calcium Signaling
/
Calcium-Calmodulin-Dependent Protein Kinase Type 2
/
Memory
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2018
Document type:
Article
Affiliation country:
China