Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro.
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.
Gillardon
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Boehringer-Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorfer St. 65, 88397 Biberach an der Riss, Germany. frank.gillardon@bc.boehringer-ingelheim.com
D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007313:Insecta; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D013058:Mass Spectrometry; D008870:Microtubules / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D020648:Peptide Elongation Factor 1 / Q000302:isolation & purification / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D020648:Peptide Elongation Factor 1; D011994:Recombinant Proteins; D014404:Tubulin; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D020558:GTP Phosphohydrolases