ArticleThe EMBO journal2004
A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 264 citations in OpenAlex.
- Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].BMC neurology · 2011Trial
- Phosphorylation-dependent regional motility of the ciliary kinesin OSM-3.The Journal of cell biology · 2025Article
- Exploring New Structures of Kinase Inhibitors and Multitarget Strategies in Alzheimer's Disease Treatment.Protein and peptide letters · 2025Review
- Phase separation of microtubule-binding proteins - implications for neuronal function and disease.Journal of cell science · 2024Review
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.Nature metabolism · 2023Article
- Tau, microtubule dynamics, and axonal transport: New paradigms for neurodegenerative disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Phosphomimetics at Ser199/Ser202/Thr205 in Tau Impairs Axonal Transport in Rat Hippocampal Neurons.Molecular neurobiology · 2023Article
- OMICS Analyses Unraveling Related Gene and Protein-Driven Molecular Mechanisms Underlying PACAP 38-Induced Neurite Outgrowth in PC12 Cells.International journal of molecular sciences · 2023Article
- c-Abl Tyrosine Kinase Is Required for BDNF-Induced Dendritic Branching and Growth.International journal of molecular sciences · 2023Article
- Editorial: Kinase/phosphatase signaling and axonal function in health and disease.Frontiers in cellular neuroscience · 2023Article
- Inhibition of MZF1/c-MYC Axis by Cantharidin Impairs Cell Proliferation in Glioblastoma.International journal of molecular sciences · 2022Article
- Tau differentially regulates the transport of early endosomes and lysosomes.Molecular biology of the cell · 2022Article
- Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer.Cell reports · 2022Article
- Tau phosphorylation and PAD exposure in regulation of axonal growth.Frontiers in cell and developmental biology · 2022Article
- Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction.Frontiers in aging neuroscience · 2022Review
- Frontotemporal Lobar Dementia Mutant Tau Impairs Axonal Transport through a Protein Phosphatase 1γ-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Deletion ofInternational journal of molecular sciences · 2021Article
- Engagement of Neurotropic Viruses in Fast Axonal Transport: Mechanisms, Potential Role of Host Kinases and Implications for Neuronal Dysfunction.Frontiers in cellular neuroscience · 2021Article
- Tau: A Signaling Hub Protein.Frontiers in molecular neuroscience · 2021Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Neuronal transmission of information requires polarized distribution of membrane proteins within axonal compartments. Membrane proteins are synthesized and packaged in membrane-bounded organelles (MBOs) in neuronal cell bodies and later transported to axons by microtubule-dependent motor proteins. Molecular mechanisms underlying targeted delivery of MBOs to discrete axonal subdomains (i.e. nodes of Ranvier or presynaptic terminals) are poorly understood, but regulatory pathways for microtubule motors may be an essential step. In this work, pharmacological, biochemical and in vivo experiments define a novel regulatory pathway for kinesin-driven motility in axons. This pathway involves enzymatic activities of cyclin-dependent kinase 5 (CDK5), protein phosphatase 1 (PP1) and glycogen synthase kinase-3 (GSK3). Inhibition of CDK5 activity in axons leads to activation of GSK3 by PP1, phosphorylation of kinesin light chains by GSK3 and detachment of kinesin from transported cargoes. We propose that regulating the activity and localization of components in this pathway allows nerve cells to target organelle delivery to specific subcellular compartments. Implications of these findings for pathogenesis of neurodegenerative diseases such as Alzheimer's disease are discussed.
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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.