title: Expanded polyglutamine stretches form an 'aggresome'.
abstract: To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with gamma-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules (MTs) with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on MTs to the MTOC, where they remain as distinct 'aggresomes''.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8181, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Shimohata
authors.forename: Aki
authors.initials: A
authors.lastname: Sato
authors.forename: James R
authors.initials: JR
authors.lastname: Burke
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Strittmatter
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019556:COS Cells; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D007202:Indicators and Reagents; D008164:Luminescent Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D022101:Microtubule-Organizing Center / Q000378:metabolism / Q000473:pathology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020191:Myoclonic Epilepsies, Progressive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010455:Peptides; D014404:Tubulin; D014746:Vimentin; C095278:atrophin-1; D049452:Green Fluorescent Proteins; C097188:polyglutamine; D015739:Nocodazole