Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization

The Journal of Biological Chemistry
M S NielsenP H Jensen

Abstract

alpha-Synuclein is a protein normally involved in presynaptic vesicle homeostasis. It participates in the development of Parkinson's disease, in which the nerve cell lesions, Lewy bodies, accumulate alpha-synuclein filaments. The synaptic neurotransmitter release is primarily dependent on Ca(2+)-regulated processes. A microdialysis technique was applied showing that alpha-synuclein binds Ca(2+) with an IC(50) of about 2-300 microm and in a reaction uninhibited by a 50-fold excess of Mg(2+). The Ca(2+)-binding site consists of a novel C-terminally localized acidic 32-amino acid domain also present in the homologue beta-synuclein, as shown by Ca(2+) binding to truncated recombinant and synthetic alpha-synuclein peptides. Ca(2+) binding affects the functional properties of alpha-synuclein. First, the ligand binding of (125)I-labeled bovine microtubule-associated protein 1A is stimulated by Ca(2+) ions in the 1-500 microm range and is dependent on an intact Ca(2+) binding site in alpha-synuclein. Second, the Ca(2+) binding stimulates the proportion of (125)I-alpha-synuclein-containing oligomers. This suggests that Ca(2+) ions may both participate in normal alpha-synuclein functions in the nerve terminal and exercise pathological ef...Continue Reading

References

Nov 1, 1992·Journal of Neurobiology·D W Choi
Aug 1, 1992·Trends in Neurosciences·K G BaimbridgeJ H Rogers
May 23, 1994·FEBS Letters·R JakesM Goedert
Aug 1, 1997·Current Opinion in Cell Biology·Y Goda, T C Südhof
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Jun 20, 1998·The Journal of Biological Chemistry·J Rizo, T C Südhof
Aug 11, 1998·Neuron·M J Berridge
Oct 3, 1998·The Journal of Biological Chemistry·P H JensenM Goedert
Oct 28, 1998·Nature·M J BerridgeP Lipp
Sep 24, 1999·Journal of Neuroscience Research·D F Clayton, J M George
Nov 17, 1999·The European Journal of Neuroscience·P H JensenC G Dotti
Jan 5, 2000·The Journal of Biological Chemistry·M OkochiC Haass
Apr 4, 2000·Nature·M B Feany, W W Bender
Jul 6, 2000·Journal of Neuroscience Research·J E DudaJ Q Trojanowski
Jul 8, 2000·Trends in Cell Biology·D Chin, A R Means
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·O CaillardA Marty
Nov 18, 2000·The Journal of Biological Chemistry·C E EllisR L Nussbaum
Feb 13, 2001·Biochemical and Biophysical Research Communications·T NakamuraS Nakamura

❮ Previous
Next ❯

Citations

Dec 20, 2012·Neurotoxicity Research·Jordan FollettDean L Pountney
Jun 14, 2005·Biochemical and Biophysical Research Communications·Xiong ZhangWeidong Le
Jun 20, 2003·Neuropharmacology·Kumlesh K DevHerman van der Putten
Apr 16, 2011·Journal of the American Chemical Society·Eva SevcsikElizabeth Rhoades
May 20, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·David R Brown
Nov 13, 2010·Metallomics : Integrated Biometal Science·Aaron Santner, Vladimir N Uversky
Aug 27, 2011·Metallomics : Integrated Biometal Science·Leonid Breydo, Vladimir N Uversky
Jul 28, 2006·The Journal of Biological Chemistry·Adrian M IsaacsBruce A Yankner
Jun 26, 2009·Molecular Biology of the Cell·Vítor L SousaEvelina Chieregatti
Jul 5, 2012·Cold Spring Harbor Perspectives in Medicine·D James SurmeierPaul T Schumacker
Feb 6, 2007·Journal of Bacteriology·Guoping RenChih-Chen Wang
Feb 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Eunsung JunnM Maral Mouradian
Nov 4, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Lucy L Liu, Katherine J Franz
Sep 27, 2014·Biomolecules·Alex Rcom-H'cheo-GauthierDean L Pountney
Apr 16, 2015·Biomolecules·Tomás Lopes da FonsecaTiago Fleming Outeiro
Apr 15, 2015·Journal of Biomolecular Structure & Dynamics·SeongByeong ParkSeokmin Shin
Jul 12, 2007·Journal of Neurochemistry·Vladimir N Uversky
Nov 26, 2013·Neurobiology of Disease·Manish Kumar Jain, Rajiv Bhat
Nov 20, 2012·Neurochemistry International·J GoodwinD L Pountney
Dec 21, 2010·Journal of Chemical Neuroanatomy·Furong ChengShun Yu
Mar 25, 2017·The Journal of Biological Chemistry·Yuichi YoshimuraFrans A A Mulder
Mar 26, 2005·Brain Research. Molecular Brain Research·Ditte LundvigPoul Henning Jensen
Jun 9, 2004·Journal of Molecular Biology·Wolfgang HoyerThomas M Jovin
Aug 8, 2007·Journal of Molecular Biology·Yoon-Hui Sung, David Eliezer
Feb 7, 2017·Journal of Neurochemistry·Alexandre N Rcom-H'cheo-GauthierDean L Pountney
Apr 24, 2004·Annals of the New York Academy of Sciences·Mario E GötzPeter Riederer
Mar 27, 2004·The Journal of Biological Chemistry·Jochen KluckenPamela J McLean
Feb 19, 2002·The Journal of Biological Chemistry·Natalie GoltsBenjamin Wolozin
Dec 14, 2004·The Journal of Biological Chemistry·Evo LinderssonPoul Henning Jensen
Aug 21, 2007·Journal of Neuroscience Research·Josephine A Wright, David R Brown
Feb 21, 2018·Nature Communications·Janin LautenschlägerGabriele S Kaminski Schierle
Mar 9, 2010·IUBMB Life·David R Brown
Aug 14, 2010·The European Journal of Neuroscience·Ayse UlusoyMarina Romero-Ramos
Feb 1, 2019·The Journal of Biological Chemistry·David Snead, David Eliezer
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Yoon-Hui Sung, David Eliezer
Mar 31, 2018·EMBO Reports·Cristine BetzerPoul Henning Jensen
Sep 26, 2015·Journal of Parkinson's Disease·Jacqueline Burré
Mar 3, 2020·Critical Reviews in Clinical Laboratory Sciences·Darren M O'HaraLorraine V Kalia

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.