ArticleCell reports2015
Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- HDAC6 inhibition alleviates mitochondrial trafficking in models of Charcot-Marie-Tooth disease type 2A.JCI insight · 2026Article
- Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?Neurobiology of disease · 2026Review
- CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer.Acta pharmaceutica Sinica. B · 2025Article
- Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons.Aging cell · 2024Article
- Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ndel1 disfavors dynein-dynactin-adaptor complex formation in two distinct ways.The Journal of biological chemistry · 2023Article
- Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ndel1 modulates dynein activation in two distinct ways.bioRxiv : the preprint server for biology · 2023Article
- c-Abl Tyrosine Kinase Is Required for BDNF-Induced Dendritic Branching and Growth.International journal of molecular sciences · 2023Article
- A phosphoswitch at acinus-serineeLife · 2022Article
- Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport.Frontiers in cell and developmental biology · 2022Review
- Casein Kinase 2 Signaling in White Matter Stroke.Frontiers in molecular biosciences · 2022Review
- Key Signature Genes of Early Terminal Granulocytic Differentiation Distinguish Sepsis From Systemic Inflammatory Response Syndrome on Intensive Care Unit Admission.Frontiers in immunology · 2022Article
- LIS1 and NDEL1 Regulate Axonal Trafficking of Mitochondria in Mature Neurons.Frontiers in molecular neuroscience · 2022Article
- Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis.Nature communications · 2021Article
- The multifaceted role of kinases in amyotrophic lateral sclerosis: genetic, pathological and therapeutic implications.Brain : a journal of neurology · 2020Review
- CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes.The Journal of cell biology · 2020Article
- Cargo-Mediated Activation of Cytoplasmic DyneinFrontiers in cell and developmental biology · 2020Review
- Sequential phosphorylation of NDEL1 by the DYRK2-GSK3β complex is critical for neuronal morphogenesis.eLife · 2019Article
- LIS1 regulates cargo-adapter-mediated activation of dynein by overcoming its autoinhibition in vivo.The Journal of cell biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration.
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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.