Camkv, short for calmodulin kinase-like vesicle-associated protein, is a pseudokinase of the CaMK family. It binds calmodulin in the presence of calcium but lacks the kinase activity typical of other CaMK family members [2]. It is predominantly expressed in brain and neural tissue, and is involved in synaptic strengthening during spatial learning by promoting dendritic spine stabilization and enrichment [4]. It may also participate in pathways related to synaptic transmission and plasticity, with its function being regulated by phosphorylation from cyclin-dependent kinase 5 (Cdk5) [3,5].

In mice, knockdown of Camkv in hippocampal CA1 pyramidal neurons impairs synaptic transmission and plasticity in vivo, leading to hyperactivity and spatial memory impairment [3]. This indicates that Camkv is crucial for dendritic spine maintenance and normal brain function. In neuroblastoma, Camkv is selectively expressed in MYCN-amplified cell lines, and its transcription is directly controlled by MYCN. It is also a potential immunotherapeutic target, and inhibition of the DYRK3/CAMKV signaling module could be an innovative treatment for neuroblastoma as both are required for neuroblastoma cell proliferation [2,6]. Additionally, CAMKV-IgG is a biomarker of immunotherapy-responsive paraneoplastic encephalitis, often associated with uterine cancer [1].

In conclusion, Camkv is essential for dendritic spine maintenance and synaptic function in the brain. Its study through mouse models has revealed its significance in neuroblastoma and paraneoplastic encephalitis. Understanding Camkv's role provides insights into the mechanisms of these diseases and may offer potential therapeutic strategies.

References:

1. Gilligan, Michael, Lesnick, Connie E, Guo, Yong, Zekeridou, Anastasia, McKeon, Andrew. 2024. Paraneoplastic Calmodulin Kinase-Like Vesicle-Associated Protein (CAMKV) Autoimmune Encephalitis. In Annals of neurology, 96, 21-33. doi:10.1002/ana.26943. https://pubmed.ncbi.nlm.nih.gov/38634529/

2. Sussman, Robyn T, Rokita, Jo Lynne, Huang, Kevin, Pawel, Bruce, Maris, John M. 2020. CAMKV Is a Candidate Immunotherapeutic Target in MYCN Amplified Neuroblastoma. In Frontiers in oncology, 10, 302. doi:10.3389/fonc.2020.00302. https://pubmed.ncbi.nlm.nih.gov/32211329/

3. Liang, Zhuoyi, Zhan, Yi, Shen, Yang, Lai, Kwok-On, Ip, Nancy Y. 2016. The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines. In Nature communications, 7, 13282. doi:10.1038/ncomms13282. https://pubmed.ncbi.nlm.nih.gov/27796283/

4. Barylko, Barbara, Hedde, Per Niklas, Taylor, Clinton A, Jameson, David M, Albanesi, Joseph P. 2022. Palmitoylation-regulated interactions of the pseudokinase calmodulin kinase-like vesicle-associated with membranes and Arc/Arg3.1. In Frontiers in synaptic neuroscience, 14, 926570. doi:10.3389/fnsyn.2022.926570. https://pubmed.ncbi.nlm.nih.gov/35965782/

5. Shah, Kavita, Rossie, Sandra. 2017. Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the Brain. In Molecular neurobiology, 55, 3426-3438. doi:10.1007/s12035-017-0525-3. https://pubmed.ncbi.nlm.nih.gov/28502042/

6. Rozen, Esteban J, Wigglesworth, Kim, Shohet, Jason M. 2024. A Novel Druggable Dual-Specificity tYrosine-Regulated Kinase3/Calmodulin Kinase-like Vesicle-Associated Signaling Module with Therapeutic Implications in Neuroblastoma. In Biomedicines, 12, . doi:10.3390/biomedicines12010197. https://pubmed.ncbi.nlm.nih.gov/38255303/