INTERACTION OF ELONGATION FACTOR 1-ALPHA WITH LEUCINE-RICH REPEAT KINASE 2 IMPAIRS KINASE ACTIVITY AND MICROTUBULE BUNDLING IN VITRO

被引:42
作者
Gillardon, F. [1 ]
机构
[1] Boehringer Ingelheim Pharma GmbH & Co KG, CNS Res, D-88397 Biberach, Germany
关键词
Parkinson's disease; leucine-rich repeat kinase 2; elongation factor 1-alpha; GTPase; microtubules; dynamics; PARKINSONS-DISEASE; FACTOR; 1A; ROC DOMAIN; LRRK2; PROTEIN; GTPASE; LEUCINE-RICH-REPEAT-KINASE-2; TRANSLOCATION; CYTOSKELETON; DEGRADATION;
D O I
10.1016/j.neuroscience.2009.06.051
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of late-onset Parkinson's disease. However, the regulators/effectors contributing to the (patho-)physiological functions of LRRK2 remain poorly defined. Here we show that human LRRK2 co-purifies/co-immunoprecipitates with elongation factor 1-alpha (EF1A). Co-incubation of recombinant LRRK2 and EF1A significantly reduces the kinase activity of LRRK2, whereas its GTPase activity remains unchanged. In addition to its canonical role in mRNA translation, EF1A maintains stability of the microtubule cytoskeleton. In the present study, EF1A promotes microtubule assembly in an in vitro tubulin polymerization assay which is impaired by co-incubation with LRRK2 at sub-stoichiometric concentrations. These findings suggest that the interaction between LRRK2 and EF1A may reciprocally modulate their physiological function. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:533 / 539
页数:7
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