Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy.

Abstract

α-Synuclein is involved in Parkinson's disease and its interaction with cell membrane is crucial to its pathological and physiological functions. Membrane properties, such as curvature and lipid composition, have been shown to affect the interactions by various techniques, but ion effects on α-synuclein membrane interactions remain elusive. Ca(2+) dynamic fluctuation in neurons plays important roles in the onset of Parkinson's disease and its influx is considered as one of the reasons to cause cell death. Using solution Nuclear Magnetic Resonance (NMR) spectroscopy, here we show that Ca(2+) can modulate α-synuclein membrane interactions through competitive binding to anionic lipids, resulting in dissociation of α-synuclein from membranes. These results suggest a negative modulatory effect of Ca(2+) on membrane mediated normal function of α-synuclein, which may provide a clue, to their dysfunction in neurodegenerative disease.

• Authors: Zeting Zhang, Chenye Dai, Jia Bai, Guohua Xu, Maili Liu, Conggang Li
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1838 Issue 3 Pg. 853-8 (Mar 2014) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24316000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• 1-palmitoyl-2-oleoyl-phosphatidyl-3-adenosine
• APOA1 protein, human
• Apolipoprotein A-I
• Glycerophospholipids
• Lipid Bilayers
• Phosphatidylcholines
• alpha-Synuclein
• Adenosine
• Calcium
• 1-palmitoyl-2-oleoylphosphatidylcholine

Topics

• Adenosine (analogs & derivatives, chemistry, metabolism)
• Apolipoprotein A-I (metabolism)
• Calcium (pharmacology)
• Cell Membrane (metabolism)
• Glycerophospholipids (chemistry, metabolism)
• Humans
• Lipid Bilayers (chemistry, metabolism)
• Magnetic Resonance Spectroscopy
• Phosphatidylcholines (chemistry, metabolism)
• Protein Binding
• alpha-Synuclein (chemistry, metabolism)