Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 4, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258356
Keywords
Mitosis; Astral microtubules; Spindle orientation; TPX2; Importin alpha; GM130; CDK1; Phosphorylation; Golgi
Categories
Funding
- Academia Sinica Career Development Award [AS-CDA109-L02]
- National Institutes of Health [GM096070, I-1910]
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This study reveals that TPX2 regulates astral microtubule growth through interaction with GM130, and the substrate preference of importin a is modulated by CDK1-mediated phosphorylation, which ultimately affects spindle orientation.
Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The orientation of the spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates astral microtubules. TPX2 in the spindle pole area is activated by GM130 (GOLGA2) on Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin alpha 1 (KPNA2) binding. Mitotic phosphorylation of importin a at serine 62 (S62) by CDK1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin alpha S62A mutation impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130-importin alpha-TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin a is regulated by CDK1-mediated phosphorylation.
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