ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Localized sphingolipid signaling at presynaptic terminals is regulated by calcium influx and promotes recruitment of priming factors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Perinatal brain developmental transition revealed by transcriptomic and proteomic analyses of Bama miniature pigs.Nature communications · 2026Article
- The Lipid Composition of the Exo-Metabolome fromMetabolites · 2025Article
- Sphingolipids modulate redox signalling during human sperm capacitation.Human reproduction (Oxford, England) · 2025Article
- Sensory modulation of neuropeptide signaling by CASY-1 gates cholinergic transmission atJournal of biosciences · 2025Article
- Cell non-autonomous signaling through the conserved C. elegans glycoprotein hormone receptor FSHR-1 regulates cholinergic neurotransmission.PLoS genetics · 2024Article
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Chemical and genetic rescue of in vivo progranulin-deficient lysosomal and autophagic defects.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
- Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer's Disease: From Physiological Performance to Pathological Impairment.Frontiers in molecular neuroscience · 2020Article
- Upregulation of human glycolipid transfer protein (GLTP) induces necroptosis in colon carcinoma cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Sphingolipidomic Analysis ofInternational journal of biological sciences · 2019Article
- Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1.Cell reports · 2018Article
- Sphingosine Kinase Regulates Neuropeptide Secretion During the Oxidative Stress-Response Through Intertissue Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Sphingosine Kinase Activates the Mitochondrial Unfolded Protein Response and Is Targeted to Mitochondria by Stress.Cell reports · 2018Article
- Sphingolipids regulate neuromuscular synapse structure and function in Drosophila.The Journal of comparative neurology · 2018Article
- The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes.Human molecular genetics · 2017Article
- Novel Mutations in Synaptic Transmission Genes Suppress Neuronal Hyperexcitation inG3 (Bethesda, Md.) · 2017Article
- Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system.British journal of pharmacology · 2017Review
- Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking.The Journal of biological chemistry · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Activity-dependent changes in presynaptic function represent a critical mechanism by which synaptic strength is controlled. However, how changes in synaptic activity couple to presynaptic components to control synaptic vesicle release and recycling are poorly understood. Sphingosine kinase (SphK) is a sphingolipid metabolic enzyme whose activity-dependent recruitment to membrane regions within presynaptic terminals promotes neurotransmitter release. Here, we show that synaptic recruitment of SPHK-1, the SphK ortholog in Caenorhabditis elegans, is mediated by presynaptic calcium influx. Quantitative fluorescence imaging of live presynaptic terminals reveals that blocking presynaptic calcium influx reduces synaptic SPHK-1 abundance whereas increasing calcium influx increases SPHK-1 synaptic abundance. CALM-1, the calcium and integrin binding protein ortholog, colocalizes with SPHK-1 at release sites and regulates muscarinic-mediated synaptic SPHK-1 recruitment. We identify two additional sphingolipid metabolic enzymes that are concentrated at presynaptic terminals, and mutants lacking one of these, HYL-1/ceramide synthase, have defects in synaptic transmission and in synaptic vesicle cycling. Finally, we show that SPHK-1 activity is required for the recruitment of the priming protein UNC-13/Munc13 to presynaptic terminals following activation by muscarinic signaling. These findings suggest that calcium-dependent regulation of local S1P metabolism at synapses may be an important mechanism by which synaptic vesicle priming factors are recruited to release sites to promote synaptic transmission.
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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 Socratic graph.