Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator
Mariana Lince-Faria1, Stefano Maffini, Bernard Orr
1Instituto de Biologia Molecular e Celular, Faculdade de Medicina, Universidade do Porto, 4150-180 Porto, Portugal.
Abstract:
A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible "wait anaphase" signal to the vicinity of the spindle.
Insights
Megator (Mtor) and Mad2 form a spindle matrix complex that regulates chromosome motion and the spindle assembly checkpoint (SAC) during mitosis. This complex ensures proper kinetochore-microtubule attachment and spindle elongation for accurate cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The existence and function of a spindle matrix in mediating chromosome motion remain debated.
- Understanding the molecular components and regulation of the mitotic spindle is crucial for cell division fidelity.
Purpose of the Study:
- To investigate the role of Megator (Mtor), a homolog of human Tpr, in mitotic spindle function.
- To determine if Mtor interacts with spindle assembly checkpoint (SAC) proteins and contributes to chromosome segregation.
Main Methods:
- Immunofluorescence and live-cell imaging in Drosophila melanogaster.
- Fluorescence recovery after photobleaching (FRAP) to assess Mtor dynamics.
- Analysis of kinetochore-microtubule attachments and mitotic progression.
Main Results:
- Mtor forms a conserved complex with Mad2 at a nuclear-derived spindle matrix.
- Mtor is retained around spindle microtubules and exhibits specific dynamic properties.
- Mtor/Tpr facilitates Mad2 and Mps1 recruitment to unattached kinetochores, ensuring proper SAC function.
- Mtor influences spindle elongation and chromosome movement during anaphase.
Conclusions:
- Mtor/Tpr acts as a spatial regulator of the SAC, promoting efficient Mad2 localization to unattached kinetochores.
- The spindle matrix, enriched with Mad2 via Mtor, confines the "wait anaphase" signal, ensuring precise mitotic timing and spindle maturation.
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