ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Protein kinase C-mediated phosphorylation of a single serine residue on the rat glial glutamine transporter SN1 governs its membrane trafficking.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. 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.
- Critical Involvement of Glial Cells in Manganese Neurotoxicity.BioMed research international · 2021Review
- The Glutamine Transporter Slc38a1 Regulates GABAergic Neurotransmission and Synaptic Plasticity.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium-dependent protein kinase 3.Molecular microbiology · 2019Article
- PKC-Mediated Modulation of Astrocyte SNAT3 Glutamine Transporter Function at Synapses in Situ.International journal of molecular sciences · 2018Article
- Article
- Regulation and function of the SLC38A3/SNAT3 glutamine transporter.Channels (Austin, Tex.) · 2016Review
- A novel method to detect articular chondrocyte death during early stages of osteoarthritis using a non-invasive ApoPep-1 probe.Arthritis research & therapy · 2015Article
- PKC-Dependent GlyT1 Ubiquitination Occurs Independent of Phosphorylation: Inespecificity in Lysine Selection for Ubiquitination.PloS one · 2015Article
- Protein kinase C-mediated phosphorylation of RKIP regulates inhibition of Na-alanine cotransport by leukotriene D(4) in intestinal epithelial cells.American journal of physiology. Cell physiology · 2014Article
- Glutamate as a neurotransmitter in the healthy brain.Journal of neural transmission (Vienna, Austria : 1996) · 2014Review
- Glutamate transporters in the biology of malignant gliomas.Cellular and molecular life sciences : CMLS · 2014Review
- Article
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
- The Amino Acid Transporters of the Glutamate/GABA-Glutamine Cycle and Their Impact on Insulin and Glucagon Secretion.Frontiers in endocrinology · 2013Review
- Protein Kinase C Phosphorylates the System N Glutamine Transporter SN1 (Slc38a3) and Regulates Its Membrane Trafficking and Degradation.Frontiers in endocrinology · 2013Review
- Manganese toxicity in the central nervous system: the glutamine/glutamate-γ-aminobutyric acid cycle.Journal of internal medicine · 2013Review
- Role of astrocytes in manganese mediated neurotoxicity.BMC pharmacology & toxicology · 2013Review
- Identification of a disulfide bridge important for transport function of SNAT4 neutral amino acid transporter.PloS one · 2013Article
- Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes.The Journal of physiology · 2012Article
- Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Molecular mechanisms involved in the replenishment of the fast neurotransmitters glutamate and GABA are poorly understood. Glutamine sustains their generation. However, glutamine formation from the recycled transmitters is confined to glial processes and requires facilitators for its translocation across the glial and neuronal membranes. Indeed, glial processes are enriched with the system N transporter SN1 (Slc38a3), which, by bidirectional transport, maintains steady extracellular glutamine levels and thereby furnishes neurons with the primary precursor for fast neurotransmitters. We now demonstrate that SN1 is phosphorylated by protein kinase Cα (PKCα) and PKCγ. Electrophysiological characterization shows that phosphorylation reduces V(max) dramatically, whereas no significant effects are seen on the K(m). Phosphorylation occurs specifically at a single serine residue (S52) in the N-terminal rat (Rattus norvegicus) SN1 and results in sequestration of the protein into intracellular reservoirs. Prolonged activation of PKC results in partial degradation of SN1. These results provide the first demonstration of phosphorylation of SN1 and regulation of its activity at the plasma membrane. Interestingly, membrane trafficking of SN1 resembles that of the glutamate transporter GLT and the glutamate-aspartate transporter GLAST: it involves the same PKC isoforms and occurs in the same glial processes. This suggests that the glutamate/GABA-glutamine cycle may be modified at two key points by similar signaling events and unmasks a prominent role for PKC-dependent phosphorylation. Our data suggest that extracellular glutamine levels may be fine-tuned by dynamic regulation of glial SN1 activity, which may impact on transmitter generation, contribute to defining quantal size, and have profound effects on synaptic plasticity.
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