ArticleThe EMBO journal2022
Endosomal phosphatidylinositol 3-phosphate controls synaptic vesicle cycling and neurotransmission.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Phosphatidylinositol-3-phosphate-dependent Klp98A recruitment regulates endosomal flux underlying developmental synaptic remodeling via Rab4.Journal of cell science · 2026Article
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity.The Journal of cell biology · 2025Article
- Biogenesis and reformation of synaptic vesicles.The Journal of physiology · 2025Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- OSBP Participates in Neural Damage Repair by Regulating Lysosome Transport Under Oxidative Stress.Molecular neurobiology · 2025Article
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Recruitment of the SNX17-Retriever recycling pathway regulates synaptic function and plasticity.The Journal of cell biology · 2023Article
- Endosomal phosphatidylinositol 3-phosphate controls synaptic vesicle cycling and neurotransmission.The EMBO journal · 2022Article
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neural circuit function requires mechanisms for controlling neurotransmitter release and the activity of neuronal networks, including modulation by synaptic contacts, synaptic plasticity, and homeostatic scaling. However, how neurons intrinsically monitor and feedback control presynaptic neurotransmitter release and synaptic vesicle (SV) recycling to restrict neuronal network activity remains poorly understood at the molecular level. Here, we investigated the reciprocal interplay between neuronal endosomes, organelles of central importance for the function of synapses, and synaptic activity. We show that elevated neuronal activity represses the synthesis of endosomal lipid phosphatidylinositol 3-phosphate [PI(3)P] by the lipid kinase VPS34. Neuronal activity in turn is regulated by endosomal PI(3)P, the depletion of which reduces neurotransmission as a consequence of perturbed SV endocytosis. We find that this mechanism involves Calpain 2-mediated hyperactivation of Cdk5 downstream of receptor- and activity-dependent calcium influx. Our results unravel an unexpected function for PI(3)P-containing neuronal endosomes in the control of presynaptic vesicle cycling and neurotransmission, which may explain the involvement of the PI(3)P-producing VPS34 kinase in neurological disease and 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.