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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 23, 2005, 25(47):10913-10921; doi:10.1523/JNEUROSCI.2922-05.2005

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 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 Web of Science (42) 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.

 Previous Article  |  Next Article 

Neurobiology of Disease
Neural Activity Controls the Synaptic Accumulation of -Synuclein

Doris L. Fortin,¹ Venu M. Nemani,¹ Susan M. Voglmaier,¹ Malcolm D. Anthony,¹ Timothy A. Ryan,² and Robert H. Edwards¹

¹Departments of Neurology and Physiology, Graduate Programs in Biomedical Sciences, Cell Biology, and Neuroscience, University of California, San Francisco, San Francisco, California 94143-2140, and ²Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021

The presynaptic protein -synuclein has a central role in Parkinson's disease (PD). However, the mechanism by which the protein contributes to neurodegeneration and its normal function remain unknown. -Synuclein localizes to the nerve terminal and interacts with artificial membranes in vitro but binds weakly to native brain membranes. To characterize the membrane association of -synuclein in living neurons, we used fluorescence recovery after photobleaching. Despite its enrichment at the synapse, -synuclein is highly mobile, with rapid exchange between adjacent synapses. In addition, we find that -synuclein disperses from the nerve terminal in response to neural activity. Dispersion depends on exocytosis, but unlike other synaptic vesicle proteins, -synuclein dissociates from the synaptic vesicle membrane after fusion. Furthermore, the dispersion of -synuclein is graded with respect to stimulus intensity. Neural activity thus controls the normal function of -synuclein at the nerve terminal and may influence its role in PD.

Key words: -synuclein; membrane association; synaptic vesicle; neural activity; Parkinson's disease; synapsin

---

Received July 14, 2005; revised September 30, 2005; accepted October 7, 2005.

This article has been cited by other articles:

				V. L. Sousa, S. Bellani, M. Giannandrea, M. Yousuf, F. Valtorta, J. Meldolesi, and E. Chieregatti {alpha}-Synuclein and Its A30P Mutant Affect Actin Cytoskeletal Structure and Dynamics Mol. Biol. Cell, August 15, 2009; 20(16): 3725 - 3739. [Abstract] [Full Text] [PDF]

				J. A. Wright, X. Wang, and D. R. Brown Unique copper-induced oligomers mediate alpha-synuclein toxicity FASEB J, August 1, 2009; 23(8): 2384 - 2393. [Abstract] [Full Text] [PDF]

				K. Nakayama, Y. Suzuki, and I. Yazawa Microtubule Depolymerization Suppresses {alpha}-Synuclein Accumulation in a Mouse Model of Multiple System Atrophy Am. J. Pathol., April 1, 2009; 174(4): 1471 - 1480. [Abstract] [Full Text] [PDF]

				K. Nakamura, V. M. Nemani, E. K. Wallender, K. Kaehlcke, M. Ott, and R. H. Edwards Optical Reporters for the Conformation of {alpha}-Synuclein Reveal a Specific Interaction with Mitochondria J. Neurosci., November 19, 2008; 28(47): 12305 - 12317. [Abstract] [Full Text] [PDF]

				S. Roy, M. J. Winton, M. M. Black, J. Q. Trojanowski, and V. M.-Y. Lee Rapid and Intermittent Cotransport of Slow Component-b Proteins J. Neurosci., March 21, 2007; 27(12): 3131 - 3138. [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]

				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]

				E. Kontopoulos, J. D. Parvin, and M. B. Feany {alpha}-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity Hum. Mol. Genet., October 15, 2006; 15(20): 3012 - 3023. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help