title: Ataxin-7 associates with microtubules and stabilizes the cytoskeletal network.
abstract: The spinocerebellar ataxia type 7 (SCA7) gene product, Ataxin-7 (ATXN7), localizes to the nucleus and has been shown to function as a component of the TATA-binding protein-free TAF-containing-SPT3-TAF9-GCN5-acetyltransferase transcription complex, although cytoplasmic localization of ATXN7 in affected neurons of human SCA7 patients has also been detected. Here, we define a physiological function for cytoplasmic ATXN7. Live imaging reveals that the intracellular distribution of ATXN7 dynamically changes and that ATXN7 distribution frequently shifts from the nucleus to the cytoplasm. Immunocytochemistry and immunoprecipitation demonstrate that cytoplasmic ATXN7 associates with microtubules (MTs), and expression of ATXN7 stabilizes MTs against nocodazole treatment, while ATXN7 knockdown enhances MT degradation. Interestingly, normal and mutant ATXN7 similarly associate with and equally stabilize MTs. Taken together, these findings provide a novel physiological function of ATXN7 in the regulation of cytoskeletal dynamics, and suggest that abnormal cytoskeletal regulation may contribute to SCA7 disease pathology.
authors.affiliation: Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tagawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oka
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Sasabe
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shiwaku
authors.forename: Albert R
authors.initials: AR
authors.lastname: La Spada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazawa
mesh_terms: D000067719:Ataxin-7; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D014404:Tubulin
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