Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase |
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Authors: | Kazumasa Aoyama Ryuzaburo Yuki Yasuyoshi Horiike Sho Kubota Noritaka Yamaguchi Mariko Morii Kenichi Ishibashi Yuji Nakayama Takahisa Kuga Yuuki Hashimoto Takeshi Tomonaga Naoto Yamaguchi |
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Affiliation: | 1. Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan;2. Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan |
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Abstract: | The non-receptor-type tyrosine kinase c-Abl is involved in actin dynamics in the cytoplasm. Having three nuclear localization signals (NLSs) and one nuclear export signal, c-Abl shuttles between the nucleus and the cytoplasm. Although monomeric actin and filamentous actin (F-actin) are present in the nucleus, little is known about the relationship between c-Abl and nuclear actin dynamics. Here, we show that nuclear-localized c-Abl induces nuclear F-actin formation. Adriamycin-induced DNA damage together with leptomycin B treatment accumulates c-Abl into the nucleus and increases the levels of nuclear F-actin. Treatment of c-Abl-knockdown cells with Adriamycin and leptomycin B barely increases the nuclear F-actin levels. Expression of nuclear-targeted c-Abl (NLS-c-Abl) increases the levels of nuclear F-actin even without Adriamycin, and the increased levels of nuclear F-actin are not inhibited by inactivation of Abl kinase activity. Intriguingly, expression of NLS-c-Abl induces the formation of long and winding bundles of F-actin within the nucleus in a c-Abl kinase activity-dependent manner. Furthermore, NLS-c-AblΔC, which lacks the actin-binding domain but has the full tyrosine kinase activity, is incapable of forming nuclear F-actin and in particular long and winding nuclear F-actin bundles. These results suggest that nuclear c-Abl plays critical roles in actin dynamics within the nucleus. |
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Keywords: | c-Abl tyrosine kinase Tyrosine phosphorylation Nucleus Actin-biding domain Actin dynamics F-actin |
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