WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin
Junjie Huang1,2, Zhuobi Liang1,2, Cuirong Guan1,2
1The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Abstract:
WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2-Aurora A-WDR62-katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics.
Insights
WDR62 protein regulates cell division by connecting TPX2-Aurora A to katanin, influencing microtubule dynamics. This discovery clarifies mechanisms behind microcephaly and spindle organization.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- WDR62 is a microcephaly-related protein associated with microtubules (MTs).
- It localizes to the spindle pole and influences spindle organization, but its precise function is unclear.
Purpose of the Study:
- To elucidate the mechanisms by which WDR62 regulates spindle dynamics.
- To identify the molecular interactions and pathways involving WDR62 in cell division.
Main Methods:
- Cellular experiments and in vitro biochemical assays were employed.
- Analysis of WDR62's interaction with microtubules, TPX2, Aurora A, and katanin.
Main Results:
- WDR62 recruits katanin to the spindle pole, forming a TPX2-Aurora A-WDR62-katanin axis.
- WDR62 binds to specific MT lattice structures and its MT-binding affinity is regulated by JNK phosphorylation.
- WDR62 acts as an adaptor, linking TPX2/Aurora A to katanin for MT severing.
Conclusions:
- WDR62 is an atypical microtubule-associated protein (MAP) that functions as a crucial adaptor.
- It plays a key role in orchestrating spindle dynamics by mediating katanin recruitment and activity.
- Understanding WDR62's function provides insights into microcephaly and spindle organization.
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