Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Iljina, Marija ^a   Tosatto, Laura ^a,d   Choi, Minee L ^b   Sang, Jason C ^a   Ye, Yu ^a,c   Hughes, Craig D ^a   Bryant, Clare E ^a   Gandhi, Sonia ^b   Klenerman, David ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c HARVARD MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF TRENTO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84988959948     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep33928     Document Type: Article

References (55)

1. Cookson, M. R. alpha-Synuclein and neuronal cell death. Molecular Neurodegeneration 4, doi: 10.1186/1750-1326-4-9 (2009).
2. Spillantini, M., et al. Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinsons disease and dementia with Lewy bodies. Neuroscience Letters 251, 205-208 (1998).
3. Conway, K., et al. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinsons disease: Implications for pathogenesis and therapy. Proceedings of the National Academy of Sciences of the United States of America 97, 571-576, doi: 10.1073/pnas.97.2.571 (2000).
4. El-Agnaf, O. & Irvine, G. Aggregation and neurotoxicity of alpha-synuclein and related peptides. Biochemical Society Transactions 30, 559-565 (2002).
5. Paleologou, K. E., Irvine, G. B. & El-Agnaf, O. M. Alpha-synuclein aggregation in neurodegenerative diseases and its inhibition as a potential therapeutic strategy. Biochem Soc Trans 33, 1106-1110, doi: 10.1042/BST20051106 (2005).
6. Iwai, A., et al. The precursor protein of non-a-beta component of Alzheimers-disease amyloid is a presynaptic protein of the central nervous system. Neuron 14, 467-475, doi: 10.1016/0896-6273(95)90302-X (1995).
7. Fauvet, B., et al. a-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem 287, 15345-15364, doi: 10.1074/jbc.M111.318949 (2012).
8. Theillet, F. X., et al. Structural disorder of monomeric a-synuclein persists in mammalian cells. Nature 530, 45-50, doi: 10.1038/nature16531 (2016).
9. Bartels, T., Choi, J. G. & Selkoe, D. J. a-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477, 107-110, doi: 10.1038/nature10324 (2011).
10. Dettmer, U., Newman, A. J., Luth, E. S., Bartels, T. & Selkoe, D. In vivo cross-linking reveals principally oligomeric forms of a-synuclein and β-synuclein in neurons and non-neural cells. J Biol Chem 288, 6371-6385, doi: 10.1074/jbc.M112.403311 (2013).
11. Westphal, C. H. & Chandra, S. S. Monomeric synucleins generate membrane curvature. J Biol Chem 288, 1829-1840, doi: 10.1074/jbc.M112.418871 (2013).
12. Gould, N., et al. Evidence of native a-synuclein conformers in the human brain. J Biol Chem 289, 7929-7934, doi: 10.1074/jbc. C113.538249 (2014).
13. Shibayama-Imazu, T., et al. Cell and tissue distribution and developmental change of neuron specific 14 kDa protein (phosphoneuroprotein 14). Brain Res 622, 17-25 (1993).
14. Bellani, S., et al. The regulation of synaptic function by alpha-synuclein. Commun Integr Biol 3, 106-109 (2010).
15. Bonini, N. M. & Giasson, B. I. Snaring the function of alpha-synuclein. Cell 123, 359-361, doi: 10.1016/j.cell.2005.10.017 (2005).
16. Wenk, M. R. & De Camilli, P. Protein-lipid interactions and phosphoinositide metabolism in membrane traffic: Insights from vesicle recycling in nerve terminals. Proceedings of the National Academy of Sciences of the United States of America 101, 8262-8269, doi: 10.1073/pnas.0401874101 (2004).
17. Rigoni, M., et al. Equivalent effects of snake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures. Science 310, 1678-1680, doi: 10.1126/science.1120640 (2005).
18. Lang, T., Halemani, N. D. & Rammner, B. Interplay between lipids and the proteinaceous membrane fusion machinery. Progress in Lipid Research 47, 461-469, doi: 10.1016/j.plipres.2008.08.002 (2008).
19. Bader, M.-F. & Vitale, N. Phospholipase D in calcium-regulated exocytosis: Lessons from chromaffin cells. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1791, 936-941, doi: 10.1016/j.bbalip.2009.02.016 (2009).
20. Sharon, R., et al. alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc Natl Acad Sci USA 98, 9110-9115, doi: 10.1073/pnas.171300598 (2001).
21. Crawford, M. A. & Sinclair, A. J. Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain. Ciba Foundation symposium, 267-292 (1971).
22. Rossetto, O., Morbiato, L., Caccin, P., Rigoni, M. & Montecucco, C. Presynaptic enzymatic neurotoxins. Journal of Neurochemistry 97, 1534-1545, doi: 10.1111/j.1471-4159.2006.03965.x (2006).
23. Perrin, R. J., Woods, W. S., Clayton, D. F. & George, J. M. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. Journal of Biological Chemistry 276, 41958-41962, doi: 10.1074/jbc.M105022200 (2001).
24. Sharon, R., et al. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinsons disease. Neuron 37, 583-595, doi: 10.1016/s0896-6273(03)00024-2 (2003).
25. Necula, M., Chirita, C. & Kuret, J. Rapid anionic micelle-mediated alpha-synuclein fibrillization in vitro. Journal of Biological Chemistry 278, 46674-46680, doi: 10.1074/jbc.M308231200 (2003).
26. Broersen, K., van den Brink, D., Fraser, G., Goedert, M. & Davletov, B. alpha-synuclein adopts an alpha-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation. Biochemistry 45, 15610-15616, doi: 10.1021/bi061743l (2006).
27. Gurry, T., et al. The dynamic structure of a-synuclein multimers. J Am Chem Soc 135, 3865-3872, doi: 10.1021/ja310518p (2013).
28. Dettmer, U., Selkoe, D. & Bartels, T. New insights into cellular a-synuclein homeostasis in health and disease. Curr Opin Neurobiol 36, 15-22, doi: 10.1016/j.conb.2015.07.007 (2016).
29. De Franceschi, G., et al. Structural and morphological characterization of aggregated species of a-synuclein induced by docosahexaenoic acid. J Biol Chem 286, 22262-22274, doi: 10.1074/jbc.M110.202937 (2011).
30. Davidson, W. S., Jonas, A., Clayton, D. F. & George, J. M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. Journal of Biological Chemistry 273, 9443-9449, doi: 10.1074/jbc.273.16.9443 (1998).
31. Ferreon, A. C., Gambin, Y., Lemke, E. A. & Deniz, A. A. Interplay of alpha-synuclein binding and conformational switching probed by single-molecule fluorescence. Proc Natl Acad Sci USA 106, 5645-5650, doi: doi: 10.1073/pnas.0809232106 (2009).
32. Middleton, E. & Rhoades, E. Effects of Curvature and Composition on alpha-Synuclein Binding to Lipid Vesicles. Biophysical Journal 99, 2279-2288, doi: 10.1016/j.bpj.2010.07.056 (2010).
33. Trexler, A. J. & Rhoades, E. Alpha-synuclein binds large unilamellar vesicles as an extended helix. Biochemistry 48, 2304-2306, doi: 10.1021/bi900114z (2009).
34. Galvagnion, C., et al. Lipid vesicles trigger a-synuclein aggregation by stimulating primary nucleation. Nat Chem Biol 11, 229-234, doi: 10.1038/nchembio.1750 (2015).
35. Cremades, N., et al. Direct observation of the interconversion of normal and toxic forms of a-synuclein. Cell 149, 1048-1059, doi: 10.1016/j.cell.2012.03.037 (2012).
36. Horrocks, M. H., et al. Fast Flow Microfluidics and Single-Molecule Fluorescence for the Rapid Characterization of a-Synuclein Oligomers. Anal Chem, doi: 10.1021/acs.analchem.5b01811 (2015).
37. Tosatto, L., et al. Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinsons disease genetically related mutants. Sci Rep 5, 16696, doi: 10.1038/srep16696 (2015).
38. Iljina, M., et al. Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading. Proc Natl Acad Sci USA, doi: 10.1073/pnas.1524128113 (2016).
39. Serth, J., Lautwein, A., Frech, M., Wittinghofer, A. & Pingoud, A. The inhibition of the GTPase activating protein-Ha-ras interaction by acidic lipids is due to physical association of the C-terminal domain of the GTPase activating protein with micellar structures. EMBO J 10, 1325-1330 (1991).
40. Serpell, L. C., Berriman, J., Jakes, R., Goedert, M. & Crowther, R. A. Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc Natl Acad Sci USA 97, 4897-4902 (2000).
41. Bennett, M. C., et al. Degradation of alpha-synuclein by proteasome. J Biol Chem 274, 33855-33858 (1999).
42. Snyder, H., et al. Aggregated and monomeric alpha-synuclein bind to the S6 proteasomal protein and inhibit proteasomal function. J Biol Chem 278, 11753-11759, doi: 10.1074/jbc.M208641200 (2003).
43. Hellstrand, E., Nowacka, A., Topgaard, D., Linse, S. & Sparr, E. Membrane lipid co-aggregation with a-synuclein fibrils. PLoS one 8, e77235, doi: 10.1371/journal.pone.0077235 (2013).
44. Brash, A. R. Arachidonic acid as a bioactive molecule. Journal of Clinical Investigation 107, 1339-1345, doi: 10.1172/jci13210 (2001).
45. Sanchez-Guajardo, V., Tentillier, N. & Romero-Ramos, M. The relation between a-synuclein and microglia in Parkinsons disease: Recent developments. Neuroscience 302, 47-58, doi: 10.1016/j.neuroscience.2015.02.008 (2015).
46. Stefanova, N., et al. Tumor necrosis factor-alpha-induced cell death in U373 cells overexpressing alpha-synuclein. J Neurosci Res 73, 334-340, doi: 10.1002/jnr.10662 (2003).
47. Meves, H. Arachidonic acid and ion channels: an update. Br J Pharmacol 155, 4-16,doi: 10.1038/bjp.2008.216 (2008).
48. Dettmer, U., et al. Parkinson-causing a-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation. Nat Commun 6, 7314, doi: 10.1038/ncomms8314 (2015).
49. Bousquet, M., et al. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinsons disease. FASEB J 22, 1213-1225, doi: 10.1096/fj.07-9677com (2008).
50. Bousquet, M., Calon, F. & Cicchetti, F. Impact of ω-3 fatty acids in Parkinsons disease. Ageing Res Rev 10, 453-463, doi: 10.1016/j. arr.2011.03.001 (2011).
51. Luth, E. S., Bartels, T., Dettmer, U., Kim, N. C. & Selkoe, D. J. Purification of a-synuclein from human brain reveals an instability of endogenous multimers as the protein approaches purity. Biochemistry 54, 279-292, doi: 10.1021/bi501188a (2015).
52. Hoyer, W., et al. Dependence of alpha-synuclein aggregate morphology on solution conditions. Journal of Molecular Biology 322, 383-393, doi: 10.1016/S0022-2836(02)00775-1 (2002).
53. Guerrero, C., Tagwerker, C., Kaiser, P. & Huang, L. An integrated mass spectrometry-based proteomic approach: quantitative analysis of tandem affinity-purified in vivo cross-linked protein complexes (QTAX) to decipher the 26 S proteasome-interacting network. Mol Cell Proteomics 5, 366-378, doi: 10.1074/mcp.M500303-MCP200 (2006).
54. Wang, X., et al. Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. Biochemistry 46, 3553-3565, doi: 10.1021/bi061994u (2007).
55. Vaarmann, A., Gandhi, S., Gourine, A. V. & Abramov, A. Y. Novel pathway for an old neurotransmitter: dopamine-induced neuronal calcium signalling via receptor-independent mechanisms. Cell Calcium 48, 176-182, doi: 10.1016/j.ceca.2010.08.008 (2010).