ArticleCell reports2015
Diminished MTORC1-Dependent JNK Activation Underlies the Neurodevelopmental Defects Associated with Lysosomal Dysfunction.
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 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells.The Journal of experimental medicine · 2025Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease.Cells · 2022Article
- Exploiting the Potential ofBiomedicines · 2021Review
- A Meta-Analysis of Bioelectric Data in Cancer, Embryogenesis, and Regeneration.Bioelectricity · 2021Article
- Evolutionary Aspects of TRPMLs and TPCs.International journal of molecular sciences · 2020Review
- The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?Frontiers in molecular neuroscience · 2020Review
- Current concepts in the neuropathogenesis of mucolipidosis type IV.Journal of neurochemistry · 2019Review
- Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses.Molecular neurodegeneration · 2019Review
- An axonal stress response pathway: degenerative and regenerative signaling by DLK.Current opinion in neurobiology · 2018Review
- Genetic strategies to tackle neurological diseases in fruit flies.Current opinion in neurobiology · 2018Review
- RPM-1 regulates axon termination by affecting growth cone collapse and microtubule stability.Development (Cambridge, England) · 2017Article
- N-butyldeoxynojirimycin delays motor deficits, cerebellar microgliosis, and Purkinje cell loss in a mouse model of mucolipidosis type IV.Neurobiology of disease · 2017Article
- Intrinsic mechanisms for axon regeneration: insights from injured axons in Drosophila.Current opinion in genetics & development · 2017Review
- Rags to riches: Amino acid sensing by the Rag GTPases in health and disease.Small GTPases · 2016Review
- Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation.Human molecular genetics · 2016Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Here, we evaluate the mechanisms underlying the neurodevelopmental deficits in Drosophila and mouse models of lysosomal storage diseases (LSDs). We find that lysosomes promote the growth of neuromuscular junctions (NMJs) via Rag GTPases and mechanistic target of rapamycin complex 1 (MTORC1). However, rather than employing S6K/4E-BP1, MTORC1 stimulates NMJ growth via JNK, a determinant of axonal growth in Drosophila and mammals. This role of lysosomal function in regulating JNK phosphorylation is conserved in mammals. Despite requiring the amino-acid-responsive kinase MTORC1, NMJ development is insensitive to dietary protein. We attribute this paradox to anaplastic lymphoma kinase (ALK), which restricts neuronal amino acid uptake, and the administration of an ALK inhibitor couples NMJ development to dietary protein. Our findings provide an explanation for the neurodevelopmental deficits in LSDs and suggest an actionable target for treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.