QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 28, 2004, 24(30):6715-6723; doi:10.1523/JNEUROSCI.1594-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (57) Citing Articles via Google Scholar Google Scholar Articles by Fortin, D. L. Articles by Edwards, R. H. Search for Related Content PubMed PubMed Citation Articles by Fortin, D. L. Articles by Edwards, R. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL FUMONISIN B1 LOVASTATIN NYSTATIN Genetics Home Reference

 Previous Article  |  Next Article 

Neurobiology of Disease
Lipid Rafts Mediate the Synaptic Localization of -Synuclein

Doris L. Fortin, Matthew D. Troyer, Ken Nakamura, Shin-ichiro Kubo, Malcolm D. Anthony, and Robert H. Edwards

Departments of Neurology and Physiology, Graduate Programs in Biomedical Sciences, Cell Biology and Neuroscience, University of California San Francisco School of Medicine, San Francisco, California 94143-2140

-Synuclein contributes to the pathogenesis of Parkinson's disease (PD), but its precise role in the disorder and its normal function remain poorly understood. Consistent with a presumed role in neurotransmitter release and its prominent deposition in the dystrophic neurites of PD, -synuclein localizes almost exclusively to the nerve terminal. In brain extracts, however, -synuclein behaves as a soluble, monomeric protein. Using a binding assay to characterize the association of -synuclein with cell membranes, we find that -synuclein binds saturably and with high affinity to characteristic intracellular structures that double label for components of lipid rafts. Biochemical analysis demonstrates the interaction of -synuclein with detergent-resistant membranes and reveals a shift in electrophoretic mobility of the raft-associated protein. In addition, the A30P mutation associated with PD disrupts the interaction of -synuclein with lipid rafts. Furthermore, we find that both the A30P mutation and raft disruption redistribute -synuclein away from synapses, indicating an important role for raft association in the normal function of -synuclein and its role in the pathogenesis of PD.

Key words: synuclein; Parkinson's disease; neurodegeneration; lipid raft; nerve terminal; synaptic localization

---

Received April 26, 2004; revised May 22, 2004; accepted June 10, 2004.

This article has been cited by other articles:

				S. Roy, M. J. Winton, M. M. Black, J. Q. Trojanowski, and V. M.-Y. Lee Cytoskeletal Requirements in Axonal Transport of Slow Component-b J. Neurosci., May 14, 2008; 28(20): 5248 - 5256. [Abstract] [Full Text] [PDF]

				A. D. Gitler, B. J. Bevis, J. Shorter, K. E. Strathearn, S. Hamamichi, L. J. Su, K. A. Caldwell, G. A. Caldwell, J.-C. Rochet, J. M. McCaffery, et al. The Parkinson's disease protein {alpha}-synuclein disrupts cellular Rab homeostasis PNAS, January 8, 2008; 105(1): 145 - 150. [Abstract] [Full Text] [PDF]

				K. Assayag, E. Yakunin, V. Loeb, D. J. Selkoe, and R. Sharon Polyunsaturated Fatty Acids Induce {alpha}-Synuclein-Related Pathogenic Changes in Neuronal Cells Am. J. Pathol., December 1, 2007; 171(6): 2000 - 2011. [Abstract] [Full Text] [PDF]

				M. Ahmad, S. Attoub, M. N. Singh, F. L. Martin, and O. M. A. El-Agnaf {gamma}-Synuclein and the progression of cancer FASEB J, November 1, 2007; 21(13): 3419 - 3430. [Abstract] [Full Text] [PDF]

				J. Jin, G. J. Li, J. Davis, D. Zhu, Y. Wang, C. Pan, and J. Zhang Identification of Novel Proteins Associated with Both {alpha}-Synuclein and DJ-1 Mol. Cell. Proteomics, May 1, 2007; 6(5): 845 - 859. [Abstract] [Full Text] [PDF]

				T. Hatano, S.-i. Kubo, S. Imai, M. Maeda, K. Ishikawa, Y. Mizuno, and N. Hattori Leucine-rich repeat kinase 2 associates with lipid rafts Hum. Mol. Genet., March 15, 2007; 16(6): 678 - 690. [Abstract] [Full Text] [PDF]

				Z. Qin, D. Hu, S. Han, S. H. Reaney, D. A. Di Monte, and A. L. Fink Effect of 4-Hydroxy-2-nonenal Modification on {alpha}-Synuclein Aggregation J. Biol. Chem., February 23, 2007; 282(8): 5862 - 5870. [Abstract] [Full Text] [PDF]

				K. E. Larsen, Y. Schmitz, M. D. Troyer, E. Mosharov, P. Dietrich, A. Z. Quazi, M. Savalle, V. Nemani, F. A. Chaudhry, R. H. Edwards, et al. {alpha}-Synuclein Overexpression in PC12 and Chromaffin Cells Impairs Catecholamine Release by Interfering with a Late Step in Exocytosis. J. Neurosci., November 15, 2006; 26(46): 11915 - 11922. [Abstract] [Full Text] [PDF]

				L. M. L. de Lau, P. J. Koudstaal, A. Hofman, and M. M. B. Breteler Serum Cholesterol Levels and the Risk of Parkinson's Disease Am. J. Epidemiol., November 15, 2006; 164(10): 998 - 1002. [Abstract] [Full Text] [PDF]

				S. Wislet-Gendebien, C. D'Souza, T. Kawarai, P. St George-Hyslop, D. Westaway, P. Fraser, and A. Tandon Cytosolic Proteins Regulate {alpha}-Synuclein Dissociation from Presynaptic Membranes J. Biol. Chem., October 27, 2006; 281(43): 32148 - 32155. [Abstract] [Full Text] [PDF]

				J. Klucken, T. F. Outeiro, P. Nguyen, P. J. McLean, and B. T. Hyman Detection of novel intracellular {alpha}-synuclein oligomeric species by fluorescence lifetime imaging FASEB J, October 1, 2006; 20(12): 2050 - 2057. [Abstract] [Full Text] [PDF]

				E. V. Mosharov, R. G. W. Staal, J. Bove, D. Prou, A. Hananiya, D. Markov, N. Poulsen, K. E. Larsen, C. M. H. Moore, M. D. Troyer, et al. {alpha}-Synuclein Overexpression Increases Cytosolic Catecholamine Concentration J. Neurosci., September 6, 2006; 26(36): 9304 - 9311. [Abstract] [Full Text] [PDF]

				A. A. Cooper, A. D. Gitler, A. Cashikar, C. M. Haynes, K. J. Hill, B. Bhullar, K. Liu, K. Xu, K. E. Strathearn, F. Liu, et al. {alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models Science, July 21, 2006; 313(5785): 324 - 328. [Abstract] [Full Text] [PDF]

				E. Rhoades, T. F. Ramlall, W. W. Webb, and D. Eliezer Quantification of {alpha}-Synuclein Binding to Lipid Vesicles Using Fluorescence Correlation Spectroscopy Biophys. J., June 15, 2006; 90(12): 4692 - 4700. [Abstract] [Full Text] [PDF]

				F. Kamp and K. Beyer Binding of {alpha}-Synuclein Affects the Lipid Packing in Bilayers of Small Vesicles J. Biol. Chem., April 7, 2006; 281(14): 9251 - 9259. [Abstract] [Full Text] [PDF]

				D. L. Fortin, V. M. Nemani, S. M. Voglmaier, M. D. Anthony, T. A. Ryan, and R. H. Edwards Neural Activity Controls the Synaptic Accumulation of {alpha}-Synuclein J. Neurosci., November 23, 2005; 25(47): 10913 - 10921. [Abstract] [Full Text] [PDF]

				S.-i. Kubo, V. M. Nemani, R. J. Chalkley, M. D. Anthony, N. Hattori, Y. Mizuno, R. H. Edwards, and D. L. Fortin A Combinatorial Code for the Interaction of {alpha}-Synuclein with Membranes J. Biol. Chem., September 9, 2005; 280(36): 31664 - 31672. [Abstract] [Full Text] [PDF]

				H.-J. Lee, S. Patel, and S.-J. Lee Intravesicular Localization and Exocytosis of {alpha}-Synuclein and its Aggregates J. Neurosci., June 22, 2005; 25(25): 6016 - 6024. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help