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Journal Article

Dynamic targeting of microtubules by TPPP/p25 affects cell survival.


Lenart,  P.
Research Group of Cytoskeletal Dynamics in Oocytes, MPI for Biophysical Chemistry, Max Planck Society;

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Lehotzky, A., Tirián, L., Tökési, N., Lenart, P., Szabó, B., Kovács, J., et al. (2004). Dynamic targeting of microtubules by TPPP/p25 affects cell survival. Journal of Cell Science, 117, 6249-6259. doi:10.1242/jcs.01550.

Cite as: http://hdl.handle.net/21.11116/0000-0002-1119-F
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.