ArticleGenes & development2012
Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
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- The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.Epilepsia open · 2025Review
- Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.Aging and disease · 2024Review
- Cell non-autonomous signaling through the conserved C. elegans glycoprotein hormone receptor FSHR-1 regulates cholinergic neurotransmission.PLoS genetics · 2024Article
- Glial Sphingosine-Mediated Epigenetic Regulation Stabilizes Synaptic Function inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture.Neurochemical research · 2022Article
- Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematode Laxus oneistus to oxic-anoxic interfaces.Scientific reports · 2022Article
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Interactome Analysis of Human Phospholipase D and Phosphatidic Acid-Associated Protein Network.Molecular & cellular proteomics : MCP · 2022Article
- Novelty of Sphingolipids in the Central Nervous System Physiology and Disease: Focusing on the Sphingolipid Hypothesis of Neuroinflammation and Neurodegeneration.International journal of molecular sciences · 2021Review
- Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment.Neuromolecular medicine · 2021Review
- Extrasynaptic acetylcholine signaling through a muscarinic receptor regulates cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- In the Model HostInternational journal of molecular sciences · 2020Article
- The muscarinic agonist arecoline suppresses motor circuit hyperactivity inmicroPublication biology · 2020Article
- Sphingosine Kinase 2 Potentiates Amyloid Deposition but Protects against Hippocampal Volume Loss and Demyelination in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Extracellular and intracellular sphingosine-1-phosphate distinctly regulates exocytosis in chromaffin cells.Journal of neurochemistry · 2019Article
- A Receptor Tyrosine Kinase Network Regulates Neuromuscular Function in Response to Oxidative Stress inGenetics · 2019Article
- Fifty years of lyase and a moment of truth: sphingosine phosphate lyase from discovery to disease.Journal of lipid research · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Sphingolipids are potent lipid second messengers that regulate cell differentiation, migration, survival, and secretion, and alterations in sphingolipid signaling have been implicated in a variety of diseases. However, how sphingolipid levels are regulated, particularly in the nervous system, remains poorly understood. Here, we show that the generation of sphingosine-1-phosphate by sphingosine kinase (SphK) promotes neurotransmitter release. Electrophysiological, imaging, and behavioral analyses of Caenorhabditis elegans mutants lacking sphingosine kinase sphk-1 indicate that neuronal development is normal, but there is a significant defect in neurotransmitter release from neuromuscular junctions. SPHK-1 localizes to discrete, nonvesicular regions within presynaptic terminals, and this localization is critical for synaptic function. Muscarinic agonists cause a rapid increase in presynaptic SPHK-1 abundance, whereas reduction of endogenous acetylcholine production results in a rapid decrease in presynaptic SPHK-1 abundance. Muscarinic regulation of presynaptic SPHK-1 abundance is mediated by a conserved presynaptic signaling pathway composed of the muscarinic acetylcholine receptor GAR-3, the heterotrimeric G protein Gαq, and its effector, Trio RhoGEF. SPHK-1 activity is required for the effects of muscarinic signaling on synaptic transmission. This study shows that SPHK-1 promotes neurotransmitter release in vivo and identifies a novel muscarinic pathway that regulates SphK abundance at presynaptic terminals.
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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.