ArticleThe EMBO journal2022
Stress-induced vesicular assemblies of dual leucine zipper kinase are signaling hubs involved in kinase activation and neurodegeneration.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Novel neuroprotective strategy based on inhibition of acute axonal palmitoylation of dual leucine-zipper kinase.Neural regeneration research · 2026Article
- Combinatorial chemistry identifies additional compounds that selectively inhibit DLK-dependent retrograde signaling while minimally affecting other axonal roles of DLK.Scientific reports · 2026Article
- Inhibiting acute, axonal DLK palmitoylation is neuroprotective and avoids deleterious effects of cell-wide DLK inhibition.Nature communications · 2025Article
- Nerve growth factor signaling tunes axon maintenance protein abundance and kinetics of Wallerian degeneration.Molecular biology of the cell · 2025Article
- Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.Nature communications · 2024Article
- Article
- Recruitment, regulation, and release: Control of signaling enzyme localization and function by reversible S-acylation.The Journal of biological chemistry · 2024Review
- Microtubules, Membranes, and Movement: New Roles for Stathmin-2 in Axon Integrity.Journal of neuroscience research · 2024Review
- Context-Specific Stress Causes Compartmentalized SARM1 Activation and Local Degeneration in Cortical Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- DLK-dependent axonal mitochondrial fission drives degeneration following axotomy.bioRxiv : the preprint server for biology · 2024Article
- Review
- The response of Dual-leucine zipper kinase (DLK) to nocodazole: Evidence for a homeostatic cytoskeletal repair mechanism.PloS one · 2024Article
- An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Stress-induced vesicular assemblies of dual leucine zipper kinase are signaling hubs involved in kinase activation and neurodegeneration.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein kinases (MAPKs) drive key signaling cascades during neuronal survival and degeneration. The localization of kinases to specific subcellular compartments is a critical mechanism to locally control signaling activity and specificity upon stimulation. However, how MAPK signaling components tightly control their localization remains largely unknown. Here, we systematically analyzed the phosphorylation and membrane localization of all MAPKs expressed in dorsal root ganglia (DRG) neurons, under control and stress conditions. We found that MAP3K12/dual leucine zipper kinase (DLK) becomes phosphorylated and palmitoylated, and it is recruited to sphingomyelin-rich vesicles upon stress. Stress-induced DLK vesicle recruitment is essential for kinase activation; blocking DLK-membrane interaction inhibits downstream signaling, while DLK recruitment to ectopic subcellular structures is sufficient to induce kinase activation. We show that the localization of DLK to newly formed vesicles is essential for local signaling. Inhibition of membrane internalization blocks DLK activation and protects against neurodegeneration in DRG neurons. These data establish vesicular assemblies as dynamically regulated platforms for DLK signaling during neuronal stress responses.
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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.