ArticleThe EMBO journal2018
Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Variable expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Pooled it
- CDKL5 deficiency impairs TBK1-mediated autophagy and clearance of neuronal protein aggregates.bioRxiv : the preprint server for biology · 2026Article
- The CDKL5 kinase undergoes liquid-liquid phase separation driven by a serine-rich C-terminal region.Life science alliance · 2026Article
- Base editing restores CDKL5 expression and rescues neuronal deficits in a patient-derived model of CDKL5 deficiency disorder.Scientific reports · 2026Article
- CDKL5 modulates the plasticity of excitatory synapses via liquid-liquid phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CDKL5 regulates the initiation of retrograde axonal transport through CLIP170-dynactin complex formation.The FEBS journal · 2026Article
- CDKL5 regulates the initiation of retrograde axonal transport through CLIP170-dynactin complex formation.The FEBS journal · 2026Article
- Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.Neurobiology of disease · 2025Article
- Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.Neurobiology of disease · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- CDKL5 Deficiency Disorder: Revealing the Molecular Mechanism of Pathogenic Variants.International journal of molecular sciences · 2025Article
- Adult-Onset Deletion of CDKL5 in Forebrain Glutamatergic Neurons Impairs Synaptic Integrity and Behavior in Mice.International journal of molecular sciences · 2025Article
- Transcriptomic Profiling of Zebrafish Mutant forInternational journal of molecular sciences · 2025Article
- A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.Neuroscience bulletin · 2025Article
- Arginylation of ⍺-tubulin at E77 regulates microtubule dynamics via MAP1S.The Journal of cell biology · 2025Article
- Arginylation of ⍺-tubulin at E77 regulates microtubule dynamics via MAP1S.The Journal of cell biology · 2025Article
- Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.Cell reports. Medicine · 2025Article
- A phylogenetic analysis of the CDKL protein family unravels its evolutionary history and supports theFrontiers in cell and developmental biology · 2025Article
- Engineered tRNAs efficiently suppress CDKL5 premature termination codons.Scientific reports · 2024Article
- Engineered tRNAs efficiently suppress CDKL5 premature termination codons.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Loss-of-function mutations in CDKL5 kinase cause severe neurodevelopmental delay and early-onset seizures. Identification of CDKL5 substrates is key to understanding its function. Using chemical genetics, we found that CDKL5 phosphorylates three microtubule-associated proteins: MAP1S, EB2 and ARHGEF2, and determined the phosphorylation sites. Substrate phosphorylations are greatly reduced in CDKL5 knockout mice, verifying these as physiological substrates. In CDKL5 knockout mouse neurons, dendritic microtubules have longer EB3-labelled plus-end growth duration and these altered dynamics are rescued by reduction of MAP1S levels through shRNA expression, indicating that CDKL5 regulates microtubule dynamics via phosphorylation of MAP1S. We show that phosphorylation by CDKL5 is required for MAP1S dissociation from microtubules. Additionally, anterograde cargo trafficking is compromised in CDKL5 knockout mouse dendrites. Finally, EB2 phosphorylation is reduced in patient-derived human neurons. Our results reveal a novel activity-dependent molecular pathway in dendritic microtubule regulation and suggest a pathological mechanism which may contribute to CDKL5 deficiency disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.