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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
Article numberddr539
Pages (from-to)1099-1110
Number of pages12
JournalHuman molecular genetics
Volume21
Issue number5
DOIs
StatePublished - Mar 2012

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