ArticleMolecular biology of the cell2022
AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4.bioRxiv : the preprint server for biology · 2026Article
- Ultrastructural studies reveal a new role for JIP3/MAPK8IP3 in endo-lysosomal maturation within the neuronal cell body.Molecular biology of the cell · 2026Article
- Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.The Journal of cell biology · 2026Article
- "Micro-managing" immune activation and protein turnover: microglial lysosomes in the context of health and disease.NPJ dementia · 2026Review
- Failure of lysosomal acidification and endomembrane network in neurodegeneration.Experimental & molecular medicine · 2025Review
- Progress on multifunctional transmembrane protein ATG9A.Cell communication and signaling : CCS · 2025Review
- Turning garbage into gold: Autophagy in synaptic function.Current opinion in neurobiology · 2025Review
- Differential roles for CLA-1L and UNC-10 in endosomal maturation and peptide release atFrontiers in molecular biosciences · 2025Article
- Organelle perturbation in Alzheimer's disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?Frontiers in cell and developmental biology · 2025Review
- Review
- The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons.Neurobiology of disease · 2024Article
- Disruptions in axonal lysosome transport and its contribution to neurological disease.Current opinion in cell biology · 2024Review
- The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.Progress in neurobiology · 2024Article
- High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia.Nature communications · 2024Article
- Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates.Nature communications · 2023Article
- A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons.Frontiers in cell and developmental biology · 2023Article
- Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization.Brain communications · 2023Article
- Loss of MAPK8IP3 Affects Endocytosis in Neurons.Frontiers in cellular neuroscience · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The adaptor protein complex-4 or AP-4 is known to mediate autophagosome maturation through regulating sorting of transmembrane cargo such as ATG9A at the Golgi. There is a need to understand AP-4 function in neurons, as mutations in any of its four subunits cause a complex form of hereditary spastic paraplegia (HSP) with intellectual disability. While AP-4 has been implicated in regulating trafficking and distribution of cargo such as ATG9A and APP, little is known about its effect on neuronal lysosomal protein traffic, lysosome biogenesis, and function. In this study, we demonstrate that in human iPSC-derived neurons AP-4 regulates lysosome composition, function, and transport via regulating the export of critical lysosomal receptors, including Sortilin 1, from the trans-Golgi network to endo-lysosomes. Additionally, loss of AP-4 causes endo-lysosomes to stall and build up in axonal swellings potentially through reduced recruitment of retrograde transport machinery to the organelle. These findings of axonal lysosome buildup are highly reminiscent of those observed in Alzheimer's disease as well as in neurons modeling the most common form of HSP, caused by
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