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Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.

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, ?CaMKII 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 ?CaMKII prevents activity-dependent expression of key genes (BDNF, c-Fos, Arc), inhibits persistent synaptic strengthening, and impairs spatial memory in vivo. Deletion of ?CaMKII in adult excitatory neurons exerts similar effects. A point mutation in ?CaMKII, 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.

SUBMITTER: Cohen SM

PROVIDER: S-EPMC6015085 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.

Cohen Samuel M SM Suutari Benjamin B He Xingzhi X Wang Yang Y Sanchez Sandrine S Tirko Natasha N NN Mandelberg Nataniel J NJ Mullins Caitlin C Zhou Guangjun G Wang Shuqi S Kats Ilona I Salah Alejandro A Tsien Richard W RW Ma Huan H

Nature communications 20180622 1

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 Ca<sup>2+</sup>/CaM to the nucleus and thus activate CREB-dependent transcription. Here we show that elimination of γCaMKII prevents activity-dependent expression of key g ...[more]

PMID: 29934532

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Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.

Publications

Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.

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