Ataxin-7 associates with microtubules and stabilizes the cytoskeletal network

Yoko Nakamura, Kazuhiko Tagawa, Tsutomu Oka, Toshikazu Sasabe, Hikaru Ito, Hiroki Shiwaku, Albert R. La spada, Hitoshi Okazawa

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29 Scopus citations


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.

Original languageEnglish (US)
Article numberddr539
Pages (from-to)1099-1110
Number of pages12
JournalHuman molecular genetics
Issue number5
StatePublished - Mar 2012

Bibliographical note

Funding Information:
This work was supported by Strategic Research Program for Brain Sciences (SRPBS) and Grant-in-Aid for Scientific Research on Innovative Areas (Foundation of Synapse and Neurocircuit Pathology) from Ministry of Education, Culture, Sports, Science and Technology of Japan, CREST from Japan Science Technology Agency and Grant-in Aid from Research Committee for Ataxic Disease from Ministry of Health, Labour and Welfare of Japan to H.O., and by NIH grant R01 EY14061 to A.R.L.


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