Aurora B-dependent phosphorylation of Ataxin-10 promotes the interaction between Ataxin-10 and Plk1 in

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCTexpansionintheATXN10gene.PreviousinvestigationshaveidentifiedthatdepletionofAtaxin-10,thegeneproduct,leadstocellularapoptosisandcytokinesisfailure.HereinweidentifythemitotickinaseAuroraBasanAtaxin-10interactingpartner.AuroraBinteractswithandphosphorylatesAtaxin-10atS12,asevidencedby in vitro kinase and mass spectrometry analysis. Both endogenous and S12-phosphorylated Ataxin-10localizes to the midbody during cytokinesis, and cytokinetic defects induced by inhibition of ATXN10expression is not rescued by the S12A mutant. Inhibition of Aurora B or expression of the S12A mutantrendersreducedinteractionbetweenAtaxin-10andpolo-likekinase1(Plk1),akinasepreviouslyidentifiedto regulate Ataxin-10 in cytokinesis. Taken together, we propose a model that Aurora B phosphorylatesAtaxin-10 at S12 to promote the interaction between Ataxin-10 and Plk1 in cytokinesis. These findingsidentify an Aurora B-dependent mechanism that implicates Ataxin-10 in cytokinesis.