title: Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2.
abstract: Construction of a mitotic spindle requires biochemical pathways to assemble spindle microtubules and structural proteins to organize these microtubules into a bipolar array. Through a complex with dynein, the receptor for hyaluronan-mediated motility (RHAMM) cross-links mitotic microtubules to provide structural support, maintain spindle integrity, and correctly orient the mitotic spindle. Here, we locate RHAMM to sites of microtubule assembly at centrosomes and non-centrosome sites near kinetochores and demonstrate that RHAMM is required for the activation of Aurora kinase A. Silencing of RHAMM delays the kinetics of spindle assembly, mislocalizes targeting protein for XKlp2 (TPX2), and attenuates the localized activation of Aurora kinase A with a consequent reduction in mitotic spindle length. The RHAMM-TPX2 complex requires a C-terminal basic leucine zipper in RHAMM and a domain that includes the nuclear localization signal in TPX2. Together, our findings identify RHAMM as a critical regulator for Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways.
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Pooja
authors.initials: P
authors.lastname: Mohan
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Jihong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Oksana
authors.initials: O
authors.lastname: Nemirovsky
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Gynaecology and Obstetrics; University Hospital Düsseldorf; Heinrich-Heine University; Düsseldorf, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Fleisch
authors.affiliation: Department of Gynaecology and Obstetrics; University Hospital Düsseldorf; Heinrich-Heine University; Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Niederacher
authors.affiliation: Department of Oncology; University of Alberta and Cross Cancer Institute; Edmonton, Alberta, Canada.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Pilarski
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: C James
authors.initials: CJ
authors.lastname: Lim
authors.affiliation: Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maxwell
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000201:enzymology*; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; C098946:hyaluronan-mediated motility receptor; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora kinase A; RHAMM; TPX2; mitosis; spindle assembly