The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines

Zhuoyi Liang, Yi Zhan, Yang Shen, Catherine C L Wong, John R. Yates, Florian Plattner, Kwok On Lai, Nancy Y. Ip

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Abstract

Dendritic spine stabilization depends on afferent synaptic input and requires changes in actin cytoskeleton dynamics and protein synthesis. However, the underlying molecular mechanism remains unclear. Here we report the identification of 'calmodulin kinase-like vesicle-associated' (CaMKv), a pseudokinase of the CaMK family with unknown function, as a synaptic protein crucial for dendritic spine maintenance. CaMKv mRNA localizes at dendrites, and its protein synthesis is regulated by neuronal activity. CaMKv function is inhibited upon phosphorylation by cyclin-dependent kinase 5 (Cdk5) at Thr345. Furthermore, CaMKv knockdown in mouse hippocampal CA1 pyramidal neurons impairs synaptic transmission and plasticity in vivo, resulting in hyperactivity and spatial memory impairment. These findings collectively indicate that the precise regulation of CaMKv through activity-dependent synthesis and post-translational phosphorylation is critical for dendritic spine maintenance, revealing an unusual signalling pathway in the regulation of synaptic transmission and brain function that involves a pseudokinase.

Original languageEnglish (US)
Article number13282
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Oct 31 2016

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Liang, Z., Zhan, Y., Shen, Y., Wong, C. C. L., Yates, J. R., Plattner, F., ... Ip, N. Y. (2016). The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines. Nature Communications, 7, [13282]. https://doi.org/10.1038/ncomms13282