Phosphorylation, lipid raft interaction and traffic of α-synuclein in a yeast model for Parkinson
نویسندگان
چکیده
Article history: Parkinson's disease is a n Received 22 December 2007 Received in revised form 8 May 2008 Accepted 2 June 2008 Available online 19 June 2008
منابع مشابه
Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner
BACKGROUND Parkinson's disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by α-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. METHODOLOGY/PRINCIPAL FINDINGS We expressed wild-type synphil...
متن کاملMolecular Determinant of α-Synuclein Pathotoxicity in Yeast Models
Parkinson disease (PD) is an incurable neurodegenerative disorder linked to the misfolding and aggregation of α-synuclein protein in dying neurons. Several molecular features of α-synuclein that appear to contribute to its properties are the familial mutant E46K, serine phosphorylation, and hydrophobic residues, but their exact role is unclear. I used two yeast models to examine how the E46K mu...
متن کاملNewly Discovered α-Synuclein Familial Mutant E46K and Key Phosphorylation and Nitrosylation-Deficient Mutants are Toxic to Yeast
Parkinson’s disease is a neurodegenerative disorder that is caused by the loss of dopaminergic neurons in the substantia nigra. Misfolding of αsynuclein is thought to cause this selective cell death. In our α-synuclein yeast overexpression model, we previously demonstrated that α synuclein, is non-toxic to yeast, runs 8-10 kDa higher on protein gels and aggregates minimally in vivo. Recently, a...
متن کاملContribution of Alanine-76 and Serine Phosphorylation in α-Synuclein Membrane Association and Aggregation in Yeasts
In Parkinson's disease (PD), misfolded and aggregated α-synuclein protein accumulates in degenerating midbrain dopaminergic neurons. The amino acid alanine-76 in α-synuclein and phosphorylation at serine-87 and serine-129 are thought to regulate its aggregation and toxicity. However, their exact contributions to α-synuclein membrane association are less clear. We found that α-synuclein is indee...
متن کاملNeurobiology of Disease Lipid Rafts Mediate the Synaptic Localization of -Synuclein
-Synuclein contributes to the pathogenesis of Parkinson’s disease (PD), but its precise role in the disorder and its normal function remain poorly understood. Consistent with a presumed role in neurotransmitter release and its prominent deposition in the dystrophic neurites of PD, -synuclein localizes almost exclusively to the nerve terminal. In brain extracts, however, -synuclein behaves as a ...
متن کامل