| alpha-Synuclein is the major component of Lewy body inclusions found in the brains of Parkinson's disease patients. We have examined the binding of alpha-synuclein to bilayers containing different amounts of negatively charged lipids using supported lipids bilayers, and epi-fluorescence microscopy. Our results show that the propensity of alpha-synuclein to cluster on the membrane increases as the concentration of anionic lipid and/or protein increases. Regions on the lipid bilayer where alpha-synuclein is clustered are also enriched in PG. We also observe divalent metal ions stimulate protein cluster formation; primarily by promoting lipid demixing. The importance of protein structure, lipid demixing, divalent ions, and mutants will be discussed as will the physiological implications. Because membrane-bound alpha-synuclein assemblies may play a role in neurotoxicity, it is of interest to determine how membranes can be used to tune the propensity of alpha-synuclein to aggregate. In addition, the role of alpha-synuclein in the formation of lipid tubules was examined. |
