title: Opposing roles for JNK and Aurora A in regulating the association of WDR62 with spindle microtubules.
abstract: WD40-repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly-associated mutations in WDR62 lead to mitotic mislocalization, highlighting a crucial requirement for precise WDR62 spatiotemporal distribution, although the regulatory mechanisms are unknown. Here, we demonstrate that the WD40-repeat region of WDR62 is required for microtubule association, whereas the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. In agreement with a functional requirement for the WDR62–JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1 (also known as MAPK8), but not JNK2 (also known as MAPK9), to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association, and loss of JNK signaling resulted in constitutive WDR62 localization to microtubules irrespective of cell cycle stage. In contrast, we identified that Aurora A kinase (AURKA) and WDR62 were in complex and that AURKA-mediated phosphorylation was required for the spindle localization of WDR62 during mitosis. Our studies highlight complex regulation of WDR62 localization, with opposing roles for JNK and AURKA in determining its spindle association.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Lim
authors.forename: Yvonne Y C
authors.initials: YY
authors.lastname: Yeap
authors.forename: Teresa T
authors.initials: TT
authors.lastname: Zhao
authors.forename: Yan Y
authors.initials: YY
authors.lastname: Yip
authors.forename: Shu C
authors.initials: SC
authors.lastname: Wong
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Ching-Seng
authors.initials: CS
authors.lastname: Ang
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Williamson
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Marie A
authors.initials: MA
authors.lastname: Bogoyevitch
authors.forename: Dominic C H
authors.initials: DC
authors.lastname: Ng
mesh_terms: D064096:Aurora Kinase A / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008870:Microtubules / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; D048055:Mitogen-Activated Protein Kinase 8