title: Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells.
abstract: Accurate spindle positioning is essential for error-free cell division. The one-cell Caenorhabditis elegans embryo has proven instrumental for dissecting mechanisms governing spindle positioning. Despite important progress, how the cortical forces that act on astral microtubules to properly position the spindle are modulated is incompletely understood. Here, we report that the PP6 phosphatase PPH-6 and its associated subunit SAPS-1, which positively regulate pulling forces acting on spindle poles, associate with the Aurora A kinase AIR-1 in C. elegans embryos. We show that acute inactivation of AIR-1 during mitosis results in excess pulling forces on astral microtubules. Furthermore, we uncover that AIR-1 acts downstream of PPH-6-SAPS-1 in modulating spindle positioning, and that PPH-6-SAPS-1 negatively regulates AIR-1 localization at the cell cortex. Moreover, we show that Aurora A and the PP6 phosphatase subunit PPP6C are also necessary for spindle positioning in human cells. There, Aurora A is needed for the cortical localization of NuMA and dynein during mitosis. Overall, our work demonstrates that Aurora A kinases and PP6 phosphatases have an ancient function in modulating spindle positioning, thus contributing to faithful cell division.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kotak
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Katayon
authors.initials: K
authors.lastname: Afshar
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Coralie
authors.initials: C
authors.lastname: Busso
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland Pierre.Gonczy@epfl.ch.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D064096:Aurora Kinase A / Q000378:metabolism*; D001696:Biomechanical Phenomena; D016203:CDC2 Protein Kinase; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; C576939:air-1 protein, C elegans; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: Aurora A kinase; Dynein; NuMA; PP6 phosphatase; Spindle positioning