ArticleNature communications2022
AP-4-mediated axonal transport controls endocannabinoid production in neurons.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4.bioRxiv : the preprint server for biology · 2026Article
- CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.JCI insight · 2026Article
- Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia.Annals of clinical and translational neurology · 2026Article
- The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B.Advances in biological regulation · 2026Article
- Dynamic Organellar Mapping in yeast reveals extensive protein localization changes during ER stress.Nature communications · 2025Article
- Uncovering cargo clients and accessory factors of AP-1 and AP-4 through vesicle proteomics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fetal and Perinatal Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia.Annals of the Child Neurology Society · 2025Article
- Article
- An accessible workflow for high-sensitivity proteomics using parallel accumulation-serial fragmentation (PASEF).Nature protocols · 2025Review
- The Spastic Paraplegia-Centers of Excellence Research Network (SP-CERN): Clinical Trial Readiness for Hereditary Spastic Paraplegia.Neurology. Genetics · 2025Article
- ATG9A vesicles are a subtype of intracellular nanovesicle.Journal of cell science · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Review
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47.EMBO molecular medicine · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Real-Time Analysis of Neuronal Cell Cultures for CNS Drug Discovery.Brain sciences · 2024Article
- AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.Nature medicine · 2024Article
- Tepsin binds LC3B to promote ATG9A trafficking and delivery.Molecular biology of the cell · 2024Article
- The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.Progress in neurobiology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and neurodegenerative disorder. Here we identify DAGLB (diacylglycerol lipase-beta), a key enzyme for generation of the endocannabinoid 2-AG (2-arachidonoylglycerol), as a cargo of AP-4 vesicles. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the trans-Golgi network of AP-4-deficient cells, that axonal DAGLB levels are reduced in neurons from a patient with AP-4 deficiency, and that 2-AG levels are reduced in the brains of AP-4 knockout mice. Importantly, we demonstrate that neurite growth defects of AP-4-deficient neurons are rescued by inhibition of MGLL (monoacylglycerol lipase), the enzyme responsible for 2-AG hydrolysis. Our study supports a new model for AP-4 deficiency syndrome in which axon growth defects arise through spatial dysregulation of endocannabinoid signalling.
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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.