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Localized Sphingolipid Signaling at Presynaptic Terminals Is Regulated by Calcium Influx and Promotes Recruitment of Priming Factors
- Source :
- The Journal of Neuroscience. 32:17909-17920
- Publication Year :
- 2012
- Publisher :
- Society for Neuroscience, 2012.
-
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 inCaenorhabditis 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.
- Subjects :
- Arecoline
Presynaptic Terminals
Cholinergic Agonists
Biology
Neurotransmission
Synaptic Transmission
Synaptic vesicle
Article
chemistry.chemical_compound
Synaptic augmentation
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Neurotransmitter
Motor Neurons
Sphingolipids
STX1A
General Neuroscience
Optical Imaging
Cell biology
Phosphotransferases (Alcohol Group Acceptor)
Synaptic fatigue
chemistry
Mutation
Synaptic plasticity
Calcium
Cholinesterase Inhibitors
Synaptic Vesicles
Carrier Proteins
Oxidoreductases
Aldicarb
Synaptic vesicle priming
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....22a103103d5ee894538f0a17afaffaac