Dynamic targeting of microtubules by TPPP/p25 affects cell survival

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 (t1/2=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.

Original languageEnglish
Pages (from-to)6249-6259
Number of pages11
JournalJournal of Cell Science
Volume117
Issue number25
DOIs
Publication statusPublished - Dec 1 2004

Fingerprint

Tubulin
Microtubules
Polymerization
Cell Survival
Proteins
Intrinsically Disordered Proteins
Fluorescence Recovery After Photobleaching
Centrosome
HeLa Cells
Mitosis
Cell Division
Fluorescent Antibody Technique
Parkinson Disease
Cell Death
Up-Regulation
Brain

Keywords

  • Aggresome
  • Cytoskeleton
  • EGFP
  • Microtubules
  • Neurodegeneration

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dynamic targeting of microtubules by TPPP/p25 affects cell survival. / Lehotzky, Atilla; Tirián, László; Tökési, Natália; Lénárt, Péter; Szabó, Bálint; Kovács, János; Ovádi, Judit.

In: Journal of Cell Science, Vol. 117, No. 25, 01.12.2004, p. 6249-6259.

Research output: Contribution to journalArticle

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AU - Kovács, János

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