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First published online November 24, 2004
doi: 10.1242/10.1242/jcs.01550

Journal of Cell Science 117, 6249-6259 (2004)
Published by The Company of Biologists 2004
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Research Article

Dynamic targeting of microtubules by TPPP/p25 affects cell survival

Atilla Lehotzky1,*, László Tirián2,*, Natália Tökési1, Péter Lénárt3, Bálint Szabó4, János Kovács5 and Judit Ovádi1,{ddagger}

1 Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1113 Budapest, Hungary
2 Department of Biology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary
3 European Molecular Biology Laboratory, 69117 Heidelberg, Germany
4 Biological Physics Research Group, Hungarian Academy of Sciences, 1117 Budapest, Hungary
5 Department of General Zoology, Eötvös University of Sciences, 1117 Budapest, Hungary

{ddagger} Author for correspondence (e-mail: ovadi{at}enzim.hu)

Accepted 21 September 2004

Recently we identified TPPP/p25 (tubulin polymerization promoting protein/p25) as a brain-specific unstructured protein that induced aberrant microtubule assemblies and ultrastructure in vitro and as a new marker for Parkinson's disease and other synucleopathies. In this paper the structural and functional consequences of TPPP/p25 are characterized to elucidate the relationship between the in vitro and the pathological phenomena. We show that at low expression levels EGFP-TPPP/p25 specifically colocalizes with the microtubule network of HeLa and NRK cells. We found that the colocalization was dynamic (tg=5 seconds by fluorescence recovery after photobleaching) and changed during the phases of mitosis. Time-lapse and immunofluorescence experiments revealed that high levels of EGFP-TPPP/p25 inhibited cell division and promoted cell death. At high expression levels or in the presence of proteosome inhibitor, green fusion protein accumulated around centrosomes forming an aggresome-like structure protruding into the nucleus or a filamentous cage of microtubules surrounding the nucleus. These structures showed high resistance to vinblastin. We propose that a potential function of TPPP/p25 is the stabilization of physiological microtubular ultrastructures, however, its upregulation may directly or indirectly initiate the formation of aberrant protein aggregates such as pathological inclusions.

Key words: Aggresome, Cytoskeleton, EGFP, Microtubules, Neurodegeneration


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