Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지

Macromolecular Crowding Enhances Interaction of ${\alpha}$-synuclein with Vesicles

  • Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Scineces, Yonsei University) ;
  • Kim, Jeonghan (School of Life Sciences and Biotechnology, Korea University) ;
  • Yi, Chi A (Department of Biomedical Laboratory Science, College of Health Scineces, Yonsei University) ;
  • Ko, Jesang (School of Life Sciences and Biotechnology, Korea University) ;
  • Park, Yong Serk (Department of Biomedical Laboratory Science, College of Health Scineces, Yonsei University) ;
  • Lee, Seung-Jae (Department of Biomedical Science and Technology, IBST, Knokuk University)
  • Received : 2012.09.25
  • Accepted : 2012.10.11
  • Published : 2012.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

${\alpha}$-synuclein (${\alpha}$-syn) is known to be implicated in the pathogenesis of Parkinson's disease and transiently bind to biological vesicles. In this study, we examined the effect of molecular crowding on the interaction of ${\alpha}$-syn with biological vesicles by using inert polymers since the environment of proteins in cells are crowded with other macromolecules. The addition of different polymers including polyethylene glycol, dextran, and ficoll enhanced the binding of ${\alpha}$-syn to vesicles in a concentration-dependent manner and the association of ${\alpha}$-syn with vesicle was proportionally augmented by increased expression of ${\alpha}$-syn. However, molecular crowding had a neglectable effect on the vesicle binding of ${\alpha}$-syn mutants (A30P, TG6), which has been reported to show impaired vesicle binding capacity. These results suggest that transient interaction of ${\alpha}$-syn with vesicles occurs more commonly in cells than expected implying interaction with vesicles may be one of the physiological processes in which ${\alpha}$-syn is involved.

Keywords

References

  1. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000. 25: 239-252. https://doi.org/10.1016/S0896-6273(00)80886-7
  2. Ben Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe DJ, Sharon R. Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic. 2009. 10: 218-234. https://doi.org/10.1111/j.1600-0854.2008.00853.x
  3. Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010. 329: 1663-1667. https://doi.org/10.1126/science.1195227
  4. Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, Lu B, Nussbaum RL. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci. 2002. 22: 8797-8807.
  5. Castagnet PI, Golovko MY, Barcelo-Coblijn GC, Nussbaum RL, Murphy EJ. Fatty acid incorporation is decreased in astrocytes cultured from alpha-synuclein gene-ablated mice. J Neurochem. 2005. 94: 839-849. https://doi.org/10.1111/j.1471-4159.2005.03247.x
  6. Cole N, Ralston GB. Enhancement of self-association of human spectrin by polyethylene glycol. Int J Biochem. 1994. 26: 799-804. https://doi.org/10.1016/0020-711X(94)90109-0
  7. Cole NB, Murphy DD, Grider T, Rueter S, Brasaemle D, Nussbaum RL. Lipid droplet binding and oligomerization properties of the Parkinson's disease protein alpha-synuclein. J Biol Chem. 2002. 277: 6344-6352. https://doi.org/10.1074/jbc.M108414200
  8. Cuneo P, Magri E, Verzola A, Grazi E. 'Macromolecular crowding' is a primary factor in the organization of the cytoskeleton. Biochem J. 1992. 281(Pt 2): 507-512. https://doi.org/10.1042/bj2810507
  9. Darios F, Ruiperez V, Lopez I, Villanueva J, Gutierrez LM, Davletov B. Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis. EMBO Rep. 2010. 11: 528-533. https://doi.org/10.1038/embor.2010.66
  10. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003. 39: 889-909. https://doi.org/10.1016/S0896-6273(03)00568-3
  11. Davidson WS, Jonas A, Clayton DF, George JM. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 1998. 273: 9443-9449. https://doi.org/10.1074/jbc.273.16.9443
  12. Ellis RJ. Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr Opin Struct Biol. 2001a. 11: 114-119. https://doi.org/10.1016/S0959-440X(00)00172-X
  13. Ellis RJ. Macromolecular crowding: obvious but underappreciated. Trends Biochem Sci. 2001b. 26: 597-604. https://doi.org/10.1016/S0968-0004(01)01938-7
  14. Elowitz MB, Surette MG, Wolf PE, Stock JB, Leibler S. Protein mobility in the cytoplasm of Escherichia coli. J Bacteriol. 1999. 181: 197-203.
  15. Forno LS. Neuropathology of Parkinson's disease. J Neuropathol Exp Neurol. 1996. 55: 259-272. https://doi.org/10.1097/00005072-199603000-00001
  16. Goedert M. Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci. 2001. 2: 492-501. https://doi.org/10.1038/35081564
  17. Golovko MY, Faergeman NJ, Cole NB, Castagnet PI, Nussbaum RL, Murphy EJ. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding. Biochemistry. 2005. 44: 8251-8259. https://doi.org/10.1021/bi0502137
  18. Hardy J, Cookson MR, Singleton A. Genes and parkinsonism. Lancet Neurol. 2003. 2: 221-228. https://doi.org/10.1016/S1474-4422(03)00350-8
  19. Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, de Silva HA, Kittel A, Saitoh T. The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron. 1995. 14: 467-475. https://doi.org/10.1016/0896-6273(95)90302-X
  20. Jo E, Darabie AA, Han K, Tandon A, Fraser PE, McLaurin J. Alpha-synuclein-synaptosomal membrane interactions: implications for fibrillogenesis. Eur J Biochem. 2004. 271: 3180-3189. https://doi.org/10.1111/j.1432-1033.2004.04250.x
  21. Kim YS, Laurine E, Woods W, Lee SJ. A novel mechanism of interaction between alpha-synuclein and biological membranes. J Mol Biol. 2006. 360: 386-397. https://doi.org/10.1016/j.jmb.2006.05.004
  22. Kim YS, Lee SJ. Increased association of alpha-synuclein to perturbed cellular membranes. J Exp Biomed Sci. 2011. 17: 167-171.
  23. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998. 18: 106-108. https://doi.org/10.1038/ng0298-106
  24. Lee HJ, Kang SJ, Lee K, Im H. Human alpha-synuclein modulates vesicle trafficking through its interaction with prenylated Rab acceptor protein 1. Biochem Biophys Res Commun. 2011. 412: 526-531. https://doi.org/10.1016/j.bbrc.2011.07.028
  25. LiCata VJ, Allewell NM. Measuring hydration changes of proteins in solution: applications of osmotic stress and structure-based calculations. Methods Enzymol. 1998. 295: 42-62.
  26. Lindner R, Ralston G. Effects of dextran on the self-association of human spectrin. Biophys Chem. 1995. 57: 15-25. https://doi.org/10.1016/0301-4622(95)00063-4
  27. Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, Narasanna A, Kolodilov N, Dauer W, Hawkins RD, Arancio O. Alphasynuclein produces a long-lasting increase in neurotransmitter release. EMBO J. 2004. 23: 4506-4516. https://doi.org/10.1038/sj.emboj.7600451
  28. Martin J, Hartl FU. The effect of macromolecular crowding on chaperonin-mediated protein folding. Proc Natl Acad Sci U S A. 1997. 94: 1107-1112. https://doi.org/10.1073/pnas.94.4.1107
  29. Minton AP. Implications of macromolecular crowding for protein assembly. Curr Opin Struct Biol. 2000. 10: 34-39. https://doi.org/10.1016/S0959-440X(99)00045-7
  30. Necula M, Chirita CN, Kuret J. Rapid anionic micelle-mediated alpha-synuclein fibrillization in vitro. J Biol Chem. 2003. 278: 46674-46680. https://doi.org/10.1074/jbc.M308231200
  31. Perrin RJ, Woods WS, Clayton DF, George JM. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J Biol Chem. 2001. 276: 41958-41962. https://doi.org/10.1074/jbc.M105022200
  32. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997. 276: 2045-2047. https://doi.org/10.1126/science.276.5321.2045
  33. Rivas G, Fernandez JA, Minton AP. Direct observation of the self-association of dilute proteins in the presence of inert macromolecules at high concentration via tracer sedimentation equilibrium: theory, experiment, and biological significance. Biochemistry. 1999. 38: 9379-9388. https://doi.org/10.1021/bi990355z
  34. Rivas G, Fernandez JA, Minton AP. Direct observation of the enhancement of noncooperative protein self-assembly by macromolecular crowding: indefinite linear self-association of bacterial cell division protein FtsZ. Proc Natl Acad Sci U S A. 2001. 98: 3150-3155. https://doi.org/10.1073/pnas.051634398
  35. Scherzer CR, Jensen RV, Gullans SR, Feany MB. Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease. Hum Mol Genet. 2003. 12: 2457-2466. https://doi.org/10.1093/hmg/ddg265
  36. Sharon R, Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron. 2003a. 37: 583-595. https://doi.org/10.1016/S0896-6273(03)00024-2
  37. Sharon R, Bar-Joseph I, Mirick GE, Serhan CN, Selkoe DJ. Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alphasynucleinopathies. J Biol Chem. 2003b. 278: 49874-49881. https://doi.org/10.1074/jbc.M309127200
  38. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. Alpha-synuclein locus triplication causes Parkinson's disease. Science. 2003. 302: 841. https://doi.org/10.1126/science.1090278
  39. Swaminathan R, Hoang CP, Verkman AS. Photobleaching recovery and anisotropy decay of green fluorescent protein GFP-S65T in solution and cells: cytoplasmic viscosity probed by green fluorescent protein translational and rotational diffusion. Biophys J. 1997. 72: 1900-1907. https://doi.org/10.1016/S0006-3495(97)78835-0
  40. van den Berg B, Ellis RJ, Dobson CM. Effects of macromolecular crowding on protein folding and aggregation. EMBO J. 1999. 18: 6927-6933. https://doi.org/10.1093/emboj/18.24.6927
  41. van den Berg B, Wain R, Dobson CM, Ellis RJ. Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell. EMBO J. 2000. 19: 3870-3875. https://doi.org/10.1093/emboj/19.15.3870
  42. Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science. 2003. 302: 1769-1772. https://doi.org/10.1126/science.1090389
  43. Yavich L, Jakala P, Tanila H. Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice. J Neurochem. 2006. 99: 724-732. https://doi.org/10.1111/j.1471-4159.2006.04098.x
  44. Yavich L, Tanila H, Vepsalainen S, Jakala P. Role of alphasynuclein in presynaptic dopamine recruitment. J Neurosci. 2004. 24: 11165-11170. https://doi.org/10.1523/JNEUROSCI.2559-04.2004
  45. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004. 55: 164-173. https://doi.org/10.1002/ana.10795
  46. Zhu M, Fink AL. Lipid binding inhibits alpha-synuclein fibril formation. J Biol Chem. 2003. 278: 16873-16877. https://doi.org/10.1074/jbc.M210136200
  47. Zhu M, Li J, Fink AL. The association of alpha-synuclein with membranes affects bilayer structure, stability, and fibril formation. J Biol Chem. 2003. 278: 40186-40197. https://doi.org/10.1074/jbc.M305326200
  48. Zimmerman SB, Minton AP. Macromolecular crowding: biochemical, biophysical, and physiological consequences. Annu Rev Biophys Biomol Struct. 1993. 22: 27-65. https://doi.org/10.1146/annurev.bb.22.060193.000331
  49. Zimmerman SB, Trach SO. Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. J Mol Biol. 1991. 222: 599-620. https://doi.org/10.1016/0022-2836(91)90499-V