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Receptor Trafficking and the Regulation of Synaptic Plasticity by SUMO

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Abstract

Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.

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References

  • Abel, T., & Lattal, K. M. (2001). Molecular mechanisms of memory acquisition, consolidation and retrieval. Current Opinion in Neurobiology, 11(2), 180–187.

    PubMed  CAS  Google Scholar 

  • Abraham, W. C., & Bear, M. F. (1996). Metaplasticity: The plasticity of synaptic plasticity. Trends in Neurosciences, 19(4), 126–130.

    PubMed  CAS  Google Scholar 

  • Anderson, D. B., Wilkinson, K. A., & Henley, J. M. (2009). Protein SUMOylation in neuropathological conditions. Drug News & Perspectives, 22(5), 255–265.

    CAS  Google Scholar 

  • Anggono, V., & Huganir, R. L. (2012). Regulation of AMPA receptor trafficking and synaptic plasticity. Current Opinion in Neurobiology, 22(3), 461–469.

    PubMed  CAS  Google Scholar 

  • Bear, M. F., & Abraham, W. C. (1996). Long-term depression in the hippocampus. Annual Review of Neuroscience, 19, 437–462.

    PubMed  CAS  Google Scholar 

  • Benson, M. D., Li, Q. J., Kieckhafer, K., Dudek, D., Whorton, M. R., Sunahara, R. K., et al. (2007). SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5. Proceedings of the National Academy of Sciences of the United States of America, 104(6), 1805–1810.

    PubMed  CAS  Google Scholar 

  • Bliss, T. V., & Collingridge, G. L. (1993). A synaptic model of memory: Long-term potentiation in the hippocampus. Nature, 361(6407), 31–39.

    PubMed  CAS  Google Scholar 

  • Bliss, T. V., & Lomo, T. (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. Journal of Physiology, 232(2), 331–356.

    PubMed  CAS  Google Scholar 

  • Casimiro, T. M., Sossa, K. G., Uzunova, G., Beattie, J. B., Marsden, K. C., & Carroll, R. C. (2011). mGluR and NMDAR activation internalize distinct populations of AMPARs. Molecular and Cellular Neuroscience, 48(2), 161–170.

    PubMed  CAS  Google Scholar 

  • Castillo, P. E. (2012). Presynaptic LTP and LTD of excitatory and inhibitory synapses. Cold Spring Harbor Perspectives in Biology, 4(2). doi:10.1101/cshperspect.a005728.

  • Chamberlain, S. E., Gonzalez-Gonzalez, I. M., Wilkinson, K. A., Konopacki, F. A., Kantamneni, S., Henley, J. M., et al. (2012). SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity. Nature Neuroscience, 15(6), 845–852.

    PubMed  CAS  Google Scholar 

  • Chao, H. W., Hong, C. J., Huang, T. N., Lin, Y. L., & Hsueh, Y. P. (2008). SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis. Journal of Cell Biology, 182(1), 141–155.

    PubMed  CAS  Google Scholar 

  • Chowdhury, S., Shepherd, J. D., Okuno, H., Lyford, G., Petralia, R. S., Plath, N., et al. (2006). Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron, 52(3), 445–459.

    PubMed  CAS  Google Scholar 

  • Cimarosti, H., Ashikaga, E., Jaafari, N., Dearden, L., Rubin, P., Wilkinson, K. A., et al. (2012). Enhanced SUMOylation and SENP-1 protein levels following oxygen and glucose deprivation in neurones. Journal of Cerebral Blood Flow and Metabolism, 32(1), 17–22.

    PubMed  CAS  Google Scholar 

  • Cimarosti, H., Lindberg, C., Bomholt, S. F., Ronn, L. C., & Henley, J. M. (2008). Increased protein SUMOylation following focal cerebral ischemia. Neuropharmacology, 54(2), 280–289.

    PubMed  CAS  Google Scholar 

  • Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010). Long-term depression in the CNS. Nature Reviews Neuroscience, 11(7), 459–473.

    PubMed  CAS  Google Scholar 

  • Conn, P. J., & Pin, J. P. (1997). Pharmacology and functions of metabotropic glutamate receptors. Annual Review of Pharmacology and Toxicology, 37, 205–237.

    PubMed  CAS  Google Scholar 

  • Craig, T. J., & Henley, J. M. (2012). Protein SUMOylation in spine structure and function. Current Opinion in Neurobiology, 22(3), 480–487.

    PubMed  CAS  Google Scholar 

  • Craig, T. J., Jaafari, N., Petrovic, M. M., Jacobs, S. C., Rubin, P. P., Mellor, J. R., et al. (2012). Homeostatic synaptic scaling is regulated by protein SUMOylation. Journal of Biological Chemistry, 287(27), 22781–22788.

    PubMed  CAS  Google Scholar 

  • Dai, X. Q., Kolic, J., Marchi, P., Sipione, S., & Macdonald, P. E. (2009). SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell excitability. Journal of Cell Science, 122(Pt 6), 775–779.

    PubMed  CAS  Google Scholar 

  • Datwyler, A. L., Lattig-Tunnemann, G., Yang, W., Paschen, W., Lee, S. L., Dirnagl, U., et al. (2011). SUMO2/3 conjugation is an endogenous neuroprotective mechanism. Journal of Cerebral Blood Flow and Metabolism, 31(11), 2152–2159.

    PubMed  CAS  Google Scholar 

  • Dutting, E., Schroder-Kress, N., Sticht, H., & Enz, R. (2011). SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b. Biochemical Journal, 435(2), 365–371.

    PubMed  Google Scholar 

  • Enz, R. (2007). The trick of the tail: Protein–protein interactions of metabotropic glutamate receptors. BioEssays, 29(1), 60–73.

    PubMed  CAS  Google Scholar 

  • Eun Jeoung, L., Sung Hee, H., Jaesun, C., Sung Hwa, S., Kwang Hum, Y., Min Kyoung, K., et al. (2008). Regulation of glycogen synthase kinase 3beta functions by modification of the small ubiquitin-like modifier. Open Biochemistry Journal, 2, 67–76.

    PubMed  Google Scholar 

  • Feliciangeli, S., Bendahhou, S., Sandoz, G., Gounon, P., Reichold, M., Warth, R., et al. (2007). Does sumoylation control K2P1/TWIK1 background K+ channels? Cell, 130, 563–569.

    PubMed  CAS  Google Scholar 

  • Feligioni, M., Nishimune, A., & Henley, J. M. (2009). Protein SUMOylation modulates calcium influx and glutamate release from presynaptic terminals. European Journal of Neuroscience, 29(7), 1348–1356.

    PubMed  Google Scholar 

  • Flavell, S. W., Cowan, C. W., Kim, T. K., Greer, P. L., Lin, Y., Paradis, S., et al. (2006). Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, 311(5763), 1008–1012.

    PubMed  CAS  Google Scholar 

  • Freund, T. F., Katona, I., & Piomelli, D. (2003). Role of endogenous cannabinoids in synaptic signaling. Physiological Reviews, 83(3), 1017–1066.

    PubMed  CAS  Google Scholar 

  • Geiss-Friedlander, R., & Melchior, F. (2007). Concepts in SUMOylation: A decade on. Nature Reviews Molecular Cell Biology, 8(12), 947–956.

    PubMed  CAS  Google Scholar 

  • Goldstein, S. A., Wang, K. W., Ilan, N., & Pausch, M. H. (1998). Sequence and function of the two P domain potassium channels: Implications of an emerging superfamily. Journal of Molecular Medicine (Berlin), 76(1), 13–20.

    CAS  Google Scholar 

  • Golebiowski, F., Matic, I., Tatham, M. H., Cole, C., Yin, Y., Nakamura, A., et al. (2009). System-wide changes to SUMO modifications in response to heat shock. Science Signaling, 2(72), ra24.

    PubMed  Google Scholar 

  • Gonzalez-Gonzalez, I. M., Konopacki, F. A., Rocca, D. L., Doherty, A. J., Jaafari, N., Wilkinson, K. A., et al. (2012). Kainate receptor trafficking. Wiley Interdisciplinary Reviews. Membrane Transport and Signaling, 1(1), 31–44.

    CAS  Google Scholar 

  • Gonzalez-Santamaria, J., Campagna, M., Ortega-Molina, A., Marcos-Villar, L., de la Cruz-Herrera, C. F., Gonzalez, D., et al. (2012). Regulation of the tumor suppressor PTEN by SUMO. Cell Death & Disease, 3, e393.

    CAS  Google Scholar 

  • Gowran, A., Murphy, C. E., & Campbell, V. A. (2009). Delta(9)-tetrahydrocannabinol regulates the p53 post-translational modifiers Murine double minute 2 and the Small Ubiquitin MOdifier protein in the rat brain. FEBS Letters, 583(21), 3412–3418.

    PubMed  CAS  Google Scholar 

  • Gregoire, S., & Yang, X. J. (2005). Association with class IIa histone deacetylases upregulates the sumoylation of MEF2 transcription factors. Molecular and Cellular Biology, 25(6), 2273–2287.

    PubMed  CAS  Google Scholar 

  • Guo, C., Hildick, K. L., Luo, J., Dearden, L., Wilkinson, K. A., & Henley, J. M. (2013). SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia. EMBO Journal, 32(11), 1514–1528.

    PubMed  CAS  Google Scholar 

  • Hay, R. T. (2005). SUMO: A history of modification. Molecular Cell, 18(1), 1–12.

    PubMed  CAS  Google Scholar 

  • Henley, J. M., Barker, E. A., & Glebov, O. O. (2011). Routes, destinations and delays: Recent advances in AMPA receptor trafficking. Trends in Neurosciences, 34(5), 258–268.

    PubMed  CAS  Google Scholar 

  • Henley, J. M., & Wilkinson, K. A. (2013). AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging. Dialogues in Clinical Neuroscience, 15(1), 11–27.

    Google Scholar 

  • Huang, J., Yan, J., Zhang, J., Zhu, S., Wang, Y., Shi, T., et al. (2012). SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane. Nature Communications, 3, 911.

    PubMed  Google Scholar 

  • Ibata, K., Sun, Q., & Turrigiano, G. G. (2008). Rapid synaptic scaling induced by changes in postsynaptic firing. Neuron, 57(6), 819–826.

    PubMed  CAS  Google Scholar 

  • Jaafari, N., Henley, J. M., & Hanley, J. G. (2012). PICK1 mediates transient synaptic expression of GluA2-lacking AMPA receptors during glycine-induced AMPA receptor trafficking. Journal of Neuroscience, 32(34), 11618–11630.

    PubMed  CAS  Google Scholar 

  • Jaafari, N., Konopacki, F. A., Owen, T. F., Kantamneni, S., Rubin, P., Craig, T. J., et al. (2013). SUMOylation is required for glycine-induced increases in AMPA receptor surface expression (ChemLTP) in hippocampal neurons. PLoS One, 8(1), e52345.

    PubMed  CAS  Google Scholar 

  • Jurado, S., Benoist, M., Lario, A., Knafo, S., Petrok, C. N., & Esteban, J. A. (2010). PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression. EMBO Journal, 29(16), 2827–2840.

    PubMed  CAS  Google Scholar 

  • Kang, J., Gocke, C. B., & Yu, H. (2006). Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity. BMC Biochemistry, 7, 5.

    PubMed  Google Scholar 

  • Kantamneni, S., Correa, S. A., Hodgkinson, G. K., Meyer, G., Vinh, N. N., Henley, J. M., et al. (2007). GISP: A novel brain-specific protein that promotes surface expression and function of GABA(B) receptors. Journal of Neurochemistry, 100(4), 1003–1017.

    PubMed  CAS  Google Scholar 

  • Kantamneni, S., Holman, D., Wilkinson, K. A., Correa, S. A., Feligioni, M., Ogden, S., et al. (2008). GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Journal of Neurochemistry, 107(1), 86–95.

    PubMed  CAS  Google Scholar 

  • Kantamneni, S., Holman, D., Wilkinson, K. A., Nishimune, A., & Henley, J. M. (2009). GISP increases neurotransmitter receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Neuroscience Letters, 452(2), 106–110.

    PubMed  CAS  Google Scholar 

  • Kantamneni, S., Wilkinson, K. A., Jaafari, N., Ashikaga, E., Rocca, D., Rubin, P., et al. (2011). Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP. Biochemical and Biophysical Research Communications, 409(4), 657–662.

    PubMed  CAS  Google Scholar 

  • Katona, I., & Freund, T. F. (2008). Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nature Medicine, 14(9), 923–930.

    PubMed  CAS  Google Scholar 

  • Katona, I., & Freund, T. F. (2012). Multiple functions of endocannabinoid signaling in the brain. Annual Review of Neuroscience, 35, 529–558.

    PubMed  CAS  Google Scholar 

  • Katzmann, D. J., Odorizzi, G., & Emr, S. D. (2002). Receptor downregulation and multivesicular-body sorting. Nature Reviews Molecular Cell Biology, 3(12), 893–905.

    PubMed  CAS  Google Scholar 

  • Kauer, J. A., & Malenka, R. C. (2007). Synaptic plasticity and addiction. Nature Reviews Neuroscience, 8(11), 844–858.

    PubMed  CAS  Google Scholar 

  • Konopacki, F. A., Jaafari, N., Rocca, D. L., Wilkinson, K. A., Chamberlain, S., Rubin, P., et al. (2011). Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis. Proceedings of the National Academy of Sciences of the United States of America, 108(49), 19772–19777.

    PubMed  CAS  Google Scholar 

  • Kullmann, D. M., Erdemli, G., & Asztely, F. (1996). LTP of AMPA and NMDA receptor-mediated signals: Evidence for presynaptic expression and extrasynaptic glutamate spill-over. Neuron, 17(3), 461–474.

    PubMed  CAS  Google Scholar 

  • Larson, J., Wong, D., & Lynch, G. (1986). Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Research, 368(2), 347–350.

    PubMed  CAS  Google Scholar 

  • Lee, Y. J., Castri, P., Bembry, J., Maric, D., Auh, S., & Hallenbeck, J. M. (2009). SUMOylation participates in induction of ischemic tolerance. Journal of Neurochemistry, 109(1), 257–267.

    PubMed  CAS  Google Scholar 

  • Lee, Y. J., Mou, Y., Maric, D., Klimanis, D., Auh, S., & Hallenbeck, J. M. (2011). Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage. PLoS ONE, 6(10), e25852.

    PubMed  CAS  Google Scholar 

  • Levy, D. I., Velazquez, H., Goldstein, S. A., & Bockenhauer, D. (2004). Segment-specific expression of 2P domain potassium channel genes in human nephron. Kidney International, 65(3), 918–926.

    PubMed  CAS  Google Scholar 

  • Lledo, P. M., Hjelmstad, G. O., Mukherji, S., Soderling, T. R., Malenka, R. C., & Nicoll, R. A. (1995). Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism. Proceedings of the National Academy of Sciences of the United States of America, 92(24), 11175–11179.

    PubMed  CAS  Google Scholar 

  • Loriol, C., Khayachi, A., Poupon, G., Gwizdek, C., & Martin, S. (2013). Activity-dependent regulation of the sumoylation machinery in rat hippocampal neurons. Biology of the Cell, 105(1), 30–45.

    PubMed  CAS  Google Scholar 

  • Loriol, C., Parisot, J., Poupon, G., Gwizdek, C., & Martin, S. (2012). Developmental regulation and spatiotemporal redistribution of the sumoylation machinery in the rat central nervous system. PLoS One, 7(3), e33757.

    PubMed  CAS  Google Scholar 

  • Lu, H., Liu, B., You, S., Xue, Q., Zhang, F., Cheng, J., et al. (2009). The activity-dependent stimuli increase SUMO modification in SHSY5Y cells. Biochemical and Biophysical Research Communications, 390(3), 872–876.

    PubMed  CAS  Google Scholar 

  • Lu, W., Man, H., Ju, W., Trimble, W. S., MacDonald, J. F., & Wang, Y. T. (2001). Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron, 29(1), 243–254.

    PubMed  CAS  Google Scholar 

  • Lynch, M. A. (2004). Long-term potentiation and memory. Physiological Reviews, 84(1), 87–136.

    PubMed  CAS  Google Scholar 

  • Malenka, R. C., & Bear, M. F. (2004). LTP and LTD: An embarrassment of riches. Neuron, 44(1), 5–21.

    PubMed  CAS  Google Scholar 

  • Malenka, R. C., Kauer, J. A., Perkel, D. J., Mauk, M. D., Kelly, P. T., Nicoll, R. A., et al. (1989). An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. Nature, 340(6234), 554–557.

    PubMed  CAS  Google Scholar 

  • Malinow, R., & Malenka, R. C. (2002). AMPA receptor trafficking and synaptic plasticity. Annual Review of Neuroscience, 25, 103–126.

    PubMed  CAS  Google Scholar 

  • Malinow, R., Schulman, H., & Tsien, R. W. (1989). Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. Science, 245, 862–866.

    PubMed  CAS  Google Scholar 

  • Martin, S., Nishimune, A., Mellor, J. R., & Henley, J. M. (2007a). SUMOylation regulates kainate-receptor-mediated synaptic transmission. Nature, 447(7142), 321–325.

    PubMed  CAS  Google Scholar 

  • Martin, S., Wilkinson, K. A., Nishimune, A., & Henley, J. M. (2007b). Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction. Nature Reviews Neuroscience, 8(12), 948–959.

    PubMed  CAS  Google Scholar 

  • Mathie, A. (2007). Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. Journal of Physiology, 578(Pt 2), 377–385.

    PubMed  CAS  Google Scholar 

  • Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346(6284), 561–564.

    PubMed  CAS  Google Scholar 

  • Murakoshi, H., & Trimmer, J. S. (1999). Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons. Journal of Neuroscience, 19(5), 1728–1735.

    PubMed  CAS  Google Scholar 

  • Nicholls, R. E., Alarcon, J. M., Malleret, G., Carroll, R. C., Grody, M., Vronskaya, S., et al. (2008). Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility. Neuron, 58(1), 104–117.

    PubMed  CAS  Google Scholar 

  • Oliet, S. H., Malenka, R. C., & Nicoll, R. A. (1997). Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron, 18(6), 969–982.

    PubMed  CAS  Google Scholar 

  • Orias, M., Velazquez, H., Tung, F., Lee, G., & Desir, G. V. (1997). Cloning and localization of a double-pore K channel, KCNK1: Exclusive expression in distal nephron segments. American Journal of Physiology, 273(4 Pt 2), F663–F666.

    PubMed  CAS  Google Scholar 

  • Palmer, C. L., Cotton, L., & Henley, J. M. (2005). The molecular pharmacology and cell biology of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacological Reviews, 57(2), 253–277.

    PubMed  CAS  Google Scholar 

  • Paoletti, P., Bellone, C., & Zhou, Q. (2013). NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nature Reviews Neuroscience, 14(6), 383–400.

    PubMed  CAS  Google Scholar 

  • Park, S., Park, J. M., Kim, S., Kim, J. A., Shepherd, J. D., Smith-Hicks, C. L., et al. (2008). Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron, 59(1), 70–83.

    PubMed  CAS  Google Scholar 

  • Peineau, S., Taghibiglou, C., Bradley, C., Wong, T. P., Liu, L., Lu, J., et al. (2007). LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron, 53(5), 703–717.

    PubMed  CAS  Google Scholar 

  • Pertwee, R. G. (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. British Journal of Pharmacology, 156(3), 397–411.

    PubMed  CAS  Google Scholar 

  • Pittaluga, A., Segantini, D., Feligioni, M., & Raiteri, M. (2005). Extracellular protons differentially potentiate the responses of native AMPA receptor subtypes regulating neurotransmitter release. British Journal of Pharmacology, 144(2), 293–299.

    PubMed  CAS  Google Scholar 

  • Plant, L. D., Dementieva, I. S., Kollewe, A., Olikara, S., Marks, J. D., & Goldstein, S. A. (2010). One SUMO is sufficient to silence the dimeric potassium channel K2P1. Proceedings of the National Academy of Sciences of the United States of America, 107(23), 10743–10748.

    PubMed  CAS  Google Scholar 

  • Plant, L. D., Dowdell, E. J., Dementieva, I. S., Marks, J. D., & Goldstein, S. A. (2011). SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons. Journal of General Physiology, 137(5), 441–454.

    PubMed  CAS  Google Scholar 

  • Pountney, D. L., Raftery, M. J., Chegini, F., Blumbergs, P. C., & Gai, W. P. (2008). NSF, Unc-18-1, dynamin-1 and HSP90 are inclusion body components in neuronal intranuclear inclusion disease identified by anti-SUMO-1-immunocapture. Acta Neuropathologica, 116(6), 603–614.

    PubMed  CAS  Google Scholar 

  • Pozo, K., & Goda, Y. (2010). Unraveling mechanisms of homeostatic synaptic plasticity. Neuron, 66(3), 337–351.

    PubMed  CAS  Google Scholar 

  • Rajan, S., Plant, L. D., Rabin, M. L., Butler, M. H., & Goldstein, S. A. (2005). Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell, 121(1), 37–47.

    PubMed  CAS  Google Scholar 

  • Rial Verde, E. M., Lee-Osbourne, J., Worley, P. F., Malinow, R., & Cline, H. T. (2006). Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron, 52(3), 461–474.

    PubMed  Google Scholar 

  • Riquelme, C., Barthel, K. K., & Liu, X. (2006). SUMO-1 modification of MEF2A regulates its transcriptional activity. Journal of Cellular and Molecular Medicine, 10(1), 132–144.

    PubMed  CAS  Google Scholar 

  • Rutherford, L. C., Nelson, S. B., & Turrigiano, G. G. (1998). BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses. Neuron, 21(3), 521–530.

    PubMed  CAS  Google Scholar 

  • Saitoh, H., & Hinchey, J. (2000). Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. Journal of Biological Chemistry, 275(9), 6252–6258.

    PubMed  CAS  Google Scholar 

  • Shalizi, A., Bilimoria, P. M., Stegmuller, J., Gaudilliere, B., Yang, Y., Shuai, K., et al. (2007). PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic morphogenesis. Journal of Neuroscience, 27(37), 10037–10046.

    PubMed  CAS  Google Scholar 

  • Shalizi, A., Gaudilliere, B., Yuan, Z., Stegmuller, J., Shirogane, T., Ge, Q., et al. (2006). A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science, 311(5763), 1012–1017.

    PubMed  CAS  Google Scholar 

  • Shepherd, J. D., & Huganir, R. L. (2007). The cell biology of synaptic plasticity: AMPA receptor trafficking. Annual Review of Cell and Developmental Biology, 23, 613–643.

    PubMed  CAS  Google Scholar 

  • Shepherd, J. D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., et al. (2006). Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron, 52(3), 475–484.

    PubMed  CAS  Google Scholar 

  • Song, M. S., Salmena, L., & Pandolfi, P. P. (2012). The functions and regulation of the PTEN tumour suppressor. Nature Reviews Molecular Cell Biology, 13(5), 283–296.

    PubMed  CAS  Google Scholar 

  • Stellwagen, D., & Malenka, R. C. (2006). Synaptic scaling mediated by glial TNF-alpha. Nature, 440(7087), 1054–1059.

    PubMed  CAS  Google Scholar 

  • Talley, E. M., Solorzano, G., Lei, Q., Kim, D., & Bayliss, D. A. (2001). Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. Journal of Neuroscience, 21(19), 7491–7505.

    PubMed  CAS  Google Scholar 

  • Tang, Z., El Far, O., Betz, H., & Scheschonka, A. (2005). Pias1 interaction and sumoylation of metabotropic glutamate receptor 8. Journal of Biological Chemistry, 280(46), 38153–38159.

    PubMed  CAS  Google Scholar 

  • Thiagarajan, T. C., Piedras-Renteria, E. S., & Tsien, R. W. (2002). α- and βCaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron, 36(6), 1103–1114.

    PubMed  CAS  Google Scholar 

  • Tirard, M., Hsiao, H. H., Nikolov, M., Urlaub, H., Melchior, F., & Brose, N. (2012). In vivo localization and identification of SUMOylated proteins in the brain of His6-HA-SUMO1 knock-in mice. Proceedings of the National Academy of Sciences of the United States of America, 109(51), 21122–21127.

    PubMed  CAS  Google Scholar 

  • Trimmer, J. S., & Rhodes, K. J. (2004). Localization of voltage-gated ion channels in mammalian brain. Annual Review of Physiology, 66, 477–519.

    PubMed  CAS  Google Scholar 

  • Turrigiano, G. G. (2008). The self-tuning neuron: Synaptic scaling of excitatory synapses. Cell, 135(3), 422–435.

    PubMed  CAS  Google Scholar 

  • Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C., & Nelson, S. B. (1998). Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature, 391(6670), 892–896.

    PubMed  CAS  Google Scholar 

  • Wang, Z., Yue, L., White, M., Pelletier, G., & Nattel, S. (1998). Differential distribution of inward rectifier potassium channel transcripts in human atrium versus ventricle. Circulation, 98(22), 2422–2428.

    PubMed  CAS  Google Scholar 

  • Waung, M. W., Pfeiffer, B. E., Nosyreva, E. D., Ronesi, J. A., & Huber, K. M. (2008). Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron, 59(1), 84–97.

    PubMed  CAS  Google Scholar 

  • Wilkinson, K. A., & Henley, J. M. (2010). Mechanisms, regulation and consequences of protein SUMOylation. Biochemical Journal, 428(2), 133–145.

    PubMed  CAS  Google Scholar 

  • Wilkinson, K. A., & Henley, J. M. (2011). Analysis of metabotropic glutamate receptor 7 as a potential substrate for SUMOylation. Neuroscience Letters, 491(3), 181–186.

    PubMed  CAS  Google Scholar 

  • Wilkinson, K. A., Konopacki, F., & Henley, J. M. (2012). Modification and movement: Phosphorylation and SUMOylation regulate endocytosis of GluK2-containing kainate receptors. Communicative & Integrative Biology, 5(2), 223–226.

    CAS  Google Scholar 

  • Wilkinson, K. A., Nakamura, Y., & Henley, J. M. (2010). Targets and consequences of protein SUMOylation in neurons. Brain Research Reviews, 64(1), 195–212.

    PubMed  CAS  Google Scholar 

  • Wilkinson, K. A., Nishimune, A., & Henley, J. M. (2008). Analysis of SUMO-1 modification of neuronal proteins containing consensus SUMOylation motifs. Neuroscience Letters, 436(2), 239–244.

    PubMed  CAS  Google Scholar 

  • Wilson, R. I., & Nicoll, R. A. (2001). Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 410(6828), 588–592.

    PubMed  CAS  Google Scholar 

  • Yamada, T., Yang, Y., Huang, J., Coppola, G., Geschwind, D. H., & Bonni, A. (2013). Sumoylated MEF2A coordinately eliminates orphan presynaptic sites and promotes maturation of presynaptic boutons. Journal of Neuroscience, 33(11), 4726–4740.

    PubMed  CAS  Google Scholar 

  • Yang, W., Sheng, H., Warner, D. S., & Paschen, W. (2008a). Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation. Journal of Cerebral Blood Flow and Metabolism, 28(5), 892–896.

    Google Scholar 

  • Yang, W., Sheng, H., Warner, D. S., & Paschen, W. (2008). Transient global cerebral ischemia induces a massive increase in protein sumoylation. Journal of Cerebral Blood Flow and Metabolism, 28(2), 269–279.

    PubMed  Google Scholar 

  • Zhao, X., Sternsdorf, T., Bolger, T. A., Evans, R. M., & Yao, T. P. (2005). Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Molecular and Cellular Biology, 25(19), 8456–8464.

    PubMed  CAS  Google Scholar 

  • Ziv, N. E., & Garner, C. C. (2004). Cellular and molecular mechanisms of presynaptic assembly. Nature Reviews Neuroscience, 5(5), 385–399.

    PubMed  CAS  Google Scholar 

  • Zucker, R. S., & Regehr, W. G. (2002). Short-term synaptic plasticity. Annual Review of Physiology, 64, 355–405.

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Prof. Ron Hay for the kind gift of SUMO-1 and SUMO-2/3 antibodies. We are grateful to the ERC, the MRC, the Wellcome Trust, the BBSRC and Marie Curie for funding.

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Authors and Affiliations

  1. School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK

    Jia Luo, Emi Ashikaga, Philip P. Rubin, Michaela J. Heimann, Keri L. Hildick, Paul Bishop, Fatima Girach, Fernando Josa-Prado, Leo T. H. Tang, Ruth E. Carmichael, Jeremy M. Henley & Kevin A. Wilkinson

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  1. Jia Luo
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  2. Emi Ashikaga
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  3. Philip P. Rubin
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  12. Kevin A. Wilkinson
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Correspondence to Kevin A. Wilkinson.

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Jia Luo and Emi Ashikaga have contributed equally to this work.

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Luo, J., Ashikaga, E., Rubin, P.P. et al. Receptor Trafficking and the Regulation of Synaptic Plasticity by SUMO. Neuromol Med 15, 692–706 (2013). https://doi.org/10.1007/s12017-013-8253-y

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  • DOI: https://doi.org/10.1007/s12017-013-8253-y

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