title: The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4.
abstract: The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5.
authors: Laboratory of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Megan M
authors: MM
authors: Gnazzo
authors: Laboratory of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Eva-Maria E
authors: EE
authors: Uhlemann
authors: Laboratory of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Alex R
authors: AR
authors: Villarreal
authors: Program in Molecular Medicine, RNA Therapeutics Institute, and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Masaki
authors: M
authors: Shirayama
authors: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705.
authors: Eddie G
authors: EG
authors: Dominguez
authors: Laboratory of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706 skop@wisc.edu.
authors: Ahna R
authors: AR
authors: Skop
mesh_terms: D000818:Animals; D000067698:Ataxin-2 / Q000378:metabolism* / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D016547:Kinesins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D000067698:Ataxin-2; D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; D016601:RNA-Binding Proteins; C114455:ZEN-4 protein, C elegans; C106207:par-5 protein, C elegans; D012313:RNA; D016547:Kinesins