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Influence of MPP + on the state of tubulin polymerisation in NGF‐differentiated PC12 cells
Author(s) -
Cappelletti Graziella,
Maggioni M. Grazia,
Maci Rosalba
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990401)56:1<28::aid-jnr4>3.0.co;2-2
Subject(s) - tubulin , chemistry , microtubule , microbiology and biotechnology , nerve growth factor , biophysics , neuroscience , biochemistry , biology , receptor
Cytoskeletal proteins have been reported as constituents of cytoplasmic inclusions typical of degenerated neurones in Parkinson's disease and, in addition, the involvement of cytoskeleton in the mechanism of action of the parkinsonism‐producing neurotoxin MPP + is emerging. Here we investigate the influence of MPP + on the dynamic behaviour of microtubules. Neurone‐like cells derived from a rat pheochromocytoma cell line (PC12) and differentiated with nerve growth factor are used as a model system. We found that sublethal doses of the neurotoxin markedly affect the state of tubulin polymerisation: polymerised tubulins significantly decreased, whereas an increase of unpolymerised α‐tubulin was observed. Since the concentration of unassembled tubulin directly regulates tubulin synthesis by a feedback mechanism, we studied α‐ and β–tubulin synthesis by metabolic labelling of PC12 cells with [ 35 S] methionine and following immunoprecipitations. The results showed the significant decrease of labelling in both the microtubule subunits in cells exposed to the neurotoxin. We suggest that the MPP + ‐induced imbalance of tubulin polymerisation and synthesis represents a novel early step in the mechanism of action of the neurotoxin. J. Neurosci. Res. 56:28–35, 1999. © 1999 Wiley‐Liss, Inc.