The NIMA kinase is required to execute stage-specific mitotic functions after initiation of mitosis
Meera Govindaraghavan1, Alisha A Lad, Stephen A Osmani
1Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA.
Abstract:
The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events.
Insights
The NIMA kinase is essential for initiating mitosis and completing cell division in Aspergillus nidulans. Partial inactivation of NIMA causes defects in spindle formation and nuclear segregation, highlighting its sequential role in mitosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The NIMA kinase (Nek family) is crucial for the G2-M transition.
- NIMA inactivation causes G2 arrest; overexpression induces mitotic events.
- NIMA-GFP localization is dynamic throughout mitosis, suggesting sequential functions.
Purpose of the Study:
- To investigate the role of NIMA in specific mitotic events beyond mitotic entry.
- To define the mitotic defects associated with partial NIMA inactivation.
Main Methods:
- Partial inactivation of NIMA in Aspergillus nidulans.
- Microscopic analysis of NIMA localization and mitotic progression.
- Assessment of spindle formation, chromatin segregation, and nuclear envelope dynamics.
Main Results:
- Partial NIMA inactivation allows mitosis initiation but leads to failure in generating two daughter nuclei in some cells.
- Defects include abnormal bipolar spindle formation, incomplete nuclear pore complex disassembly, and failed chromatin segregation.
- Mitotic progression in cells with inadequate NIMA relies on the spindle assembly checkpoint, indicating significant defects.
Conclusions:
- NIMA is indispensable not only for initiating mitosis but also for the sequential completion of stage-specific mitotic events.
- NIMA's sequential functions are critical for successful cell division, including spindle assembly and nuclear segregation.
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