The dynamic instability of microtubules is required for aggresome formation in oligodendroglial cells after proteolytic stress.
University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111 Oldenburg, Germany Ubiquitinated tau-positive inclusion bodies in oligodendrocytes are consistent features in a variety of neurodegenerative disorders, and their formation points to an underlying incapacity of the protein quality control system that normally prevents the accumulation of misfolded proteins. To study the consequences of proteasomal impairment, we have used an oligodendroglial cell line, namely OLN-t40 cells, genetically engineered to express the longest human tau isoform. Treatment of OLN-t40 cells with the proteasomal inhibitor MG-132 (0.5 microM, 18 h) caused the formation of large, nonfibrillary tau-positive aggregates containing the small HSP alphaB-crystallin and ubiquitin in the vicinity of the microtubule organizing center (MTOC). The sequestration of misfolded proteins into specialized regions, called aggresomes, in response to stress stimuli has been reported to be associated with a redistribution of intermediate filaments (IFs). In oligodendroglial cells, which do not contain a cytoplasmic IF system, aggresomelike inclusions were instead surrounded by bundles of MTs and contained clusters of mitochondria. Aggresome formation was prevented by both MT-stabilizing and -destabilizing drugs, indicating not only that an intact cytoskeleton but also the dynamic instability of the MT network is required. Furthermore, the binding of stress-induced alphaBcrystallin to the MTs points to a possible protective role during disease progression.
Bauer
Nina G
NG
University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111 Oldenburg, Germany.
Richter-Landsberg
Christiane
C
D017398:Alternative Splicing; D002460:Cell Line; D003459:Crystallins / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007976:Leupeptins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D015739:Nocodazole / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D017239:Paclitaxel / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D050257:Tubulin Modulators / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D003459:Crystallins; D015853:Cysteine Proteinase Inhibitors; D006360:Heat-Shock Proteins; D007976:Leupeptins; D020033:Protein Isoforms; D050257:Tubulin Modulators; D025801:Ubiquitin; D016875:tau Proteins; D017239:Paclitaxel; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D015739:Nocodazole