title: The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines.
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.
authors: Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.|Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.|State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Zhuoyi
authors: Z
authors: Liang
authors: Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.|Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.|State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Yi
authors: Y
authors: Zhan
authors: Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.|Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.|State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Yang
authors: Y
authors: Shen
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors: Catherine C L
authors: CC
authors: Wong
authors: State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.|Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors: John R
authors: 0000-0001-5267-1672
authors: JR
authors: Yates
authors: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
authors: Florian
authors: F
authors: Plattner
authors: Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.|Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.|State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Kwok-On
authors: KO
authors: Lai
authors: Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.|Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.|State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors: Nancy Y
authors: NY
authors: Ip
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses; D009435:Synaptic Transmission; D013574:Synaptosomes / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: C000628306:CaMKv protein, mouse; D002148:Calmodulin-Binding Proteins; C085290:Camkv protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein