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WD40-Repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly mutations lead to mitotic mislocalization highlighting a critical 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 while the disordered C-terminal region regulates cell-cycle dependent compartmentation. In agreement with a functional requirement for WDR62/JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1, but not JNK2, to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association and loss of JNK signalling 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 AURKA-mediated phosphorylation was required for 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.

Opposing roles for JNK and Aurora A in regulating WD40-Repeat Protein 62 association with spindle microtubules