期刊
NEUROBIOLOGY OF DISEASE
卷 26, 期 3, 页码 521-531出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.01.014
关键词
alpha-synuclein; tau; actin; cytoskeleton; neurodegeneration; plasma membrane; Alzheimer's disease; Parkinson's disease; FRET; FLIM
alpha-Synuclein is a primarily neuronal protein that is enriched at the presynapse. alpha-Synuclein and the microtubule binding protein tau have been implicated in neurodegenerative diseases. alpha-Synuclein is known to associate with phospholipid vesicles, regulates dopamine metabolism and exhibits chaperone activity, but its main role remains largely unknown. Furthermore, knowledge on its interactions and posttranslational modifications is essential for a molecular understanding of alpha-synucleinopathies. We investigated alpha-synuclein mutations, causative for autosomal dominant forms of Parkinson's disease (A30P, A53T and E46K), and phosphorylation mutants at serine 129 (S129A and S129D) using fluorescently labelled alpha-synuclein, actin and tau. The investigation of colocalizafion, and protein-protein interactions by Forster resonance energy transfer and fluorescence lifetime imaging showed that alpha-synuclein associates with the actin cytoskeleton and interacts with tau. The A30P mutation and cytoskeletal destabilization decreased this interaction. Given the concurrent loss of membrane binding by this mutation, we propose a membrane- bound functional complex with tau that might involve the actin cytoskeleton. (c) 2007 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据