Abstract
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Previous investigations have identified that depletion of Ataxin-10, the gene product, leads to cellular apoptosis and cytokinesis failure. Herein we identify the mitotic kinase Aurora B as an Ataxin-10 interacting partner. Aurora B interacts with and phosphorylates Ataxin-10 at S12, as evidenced by in vitro kinase and mass spectrometry analysis. Both endogenous and S12-phosphorylated Ataxin-10 localizes to the midbody during cytokinesis, and cytokinetic defects induced by inhibition of ATXN10 expression is not rescued by the S12A mutant. Inhibition of Aurora B or expression of the S12A mutant renders reduced interaction between Ataxin-10 and polo-like kinase 1 (Plk1), a kinase previously identified to regulate Ataxin-10 in cytokinesis. Taken together, we propose a model that Aurora B phosphorylates Ataxin-10 at S12 to promote the interaction between Ataxin-10 and Plk1 in cytokinesis. These findings identify an Aurora B-dependent mechanism that implicates Ataxin-10 in cytokinesis.
Highlights
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene
During our previous investigation of the interaction between Ataxin-10 and Plk[115], we inadvertently identified the association between endogenous Ataxin-10 and Aurora B (Fig. 1A)
Given that we previously showed that Ataxin-10 was phosphorylated by Plk[113], we sought to delineate the relationship of Aurora B and Plk[1] in terms of regulating Ataxin-10 in cytokinesis by cytology
Summary
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Aurora B interacts with and phosphorylates Ataxin-10 at S12, as evidenced by in vitro kinase and mass spectrometry analysis Both endogenous and S12-phosphorylated Ataxin-10 localizes to the midbody during cytokinesis, and cytokinetic defects induced by inhibition of ATXN10 expression is not rescued by the S12A mutant. Aurora B is a critical component of the chromosome passenger complex, which orchestrates key events of the mitotic process, including chromosome-microtubule attachment, spindle assembly checkpoint activation, cytokinesis and eventual absciswww.nature.com/scientificreports sion[16,17]. We show that both endogenous and Aurora B-phosphorylated Ataxin-10 localizes to the midbody. Our results delineate the role of Aurora B and Plk[1] in regulating Ataxin-10 in cytokinesis
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