Protein -Protein Interactions of Synucleins: Implications for Normal Function and Neurodegenerative Disease
Payton, Jacqueline Elise
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/86641
Description
Title
Protein -Protein Interactions of Synucleins: Implications for Normal Function and Neurodegenerative Disease
Author(s)
Payton, Jacqueline Elise
Issue Date
2002
Doctoral Committee Chair(s)
George, Julia M.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Neuroscience
Language
eng
Abstract
Synucleins are a family of three small, highly conserved proteins expressed presynaptically in the central and peripheral nervous systems. The three isoforms, alpha, beta, and gamma, are most homologous in their N-terminal ∼100 residues, which form a lipid-binding amphipathic alpha-helix. Alpha-synuclein (AS) has been implicated in learning and memory and neurodegenerative disease, thereby influencing the entire spectrum of brain function. The data presented here addresses the normal function of the synucleins as it relates to protein-protein interactions. Immunoprecipitation assays reveal that AS interacts specifically with many other proteins. The most robust of these interactions is with tubulin heterodimers; however AS does not bind to polymerized microtubules. AS also interacts with, and competitively inhibits (Ki = 21nM) Phospholipase D2 (PLD2), a phosphatidylcholine-specific phosphohydrolase that is involved in cell signaling, vesicle transport, and mitogenesis. Alpha-synuclein's inhibitory capacity is dependent upon a lipid vesicle-induced conformational shift to alpha-helix. Inhibition of PLD2 also requires a portion of the acidic C-terminus, which may directly interact with PLD2. Furthermore, inhibition may be regulated by phosphorylation of specific serine or tyrosine residues in the C-terminus. These data suggest that the interaction between AS and PLD2 is a two-step process that requires an alpha-helical conformation and a direct interaction between AS and PLD2. Finally, previous work has demonstrated that the fatty acid, arachidonate, accelerates AS self-association, a process that may be involved in Parkinson's disease. The final chapter presented here shows that arachidonate also interferes with alpha-synuclein's inhibition of PLD2.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
