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

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 pseudok...

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Published in:Nature communications 2016-10, Vol.7 (1), p.13282-13282, Article 13282
Main Authors: Liang, Zhuoyi, Zhan, Yi, Shen, Yang, Wong, Catherine C. L., Yates, John R., Plattner, Florian, Lai, Kwok-On, Ip, Nancy Y.
Format: Article
Language:English
Subjects:
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Cyclin-dependent kinases
Humanities and Social Sciences
Intellectual disabilities
Kinases
Life sciences
Mass spectrometry
Morphogenesis
Morphology
multidisciplinary
Neurosciences
Phosphorylation
Protein synthesis
Proteins
Science
Science (multidisciplinary)
Scientific imaging
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Summary: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. CaMKv is a pseduokinase of unknown function. Here, the authors identify the protein as a substrate of the protein kinase Cdk5, and show that CaMKv is synthesized in response to neural activity and plays an important role in maintaining dendritic spines, synaptic plasticity, and hippocampal memory via RhoA inhibition.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms13282