McLellan Melissa M, Aerne Birgit L, Banerjee Dhoul Jennifer J, Holder Maxine V, Auchynnikava Tania, Tapon Nicolas
Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Proteomics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
EMBO J. 2025 May;44(10):2949-2975. doi: 10.1038/s44318-025-00420-5. Epub 2025 Apr 1.
Correct mitotic spindle alignment is essential for tissue architecture and plays an important role in cell fate specification through asymmetric cell division. Spindle tethering factors such as Drosophila Mud (NuMA in mammals) are recruited to the cell cortex and capture astral microtubules, pulling the spindle in the correct orientation. However, how spindle tethering complexes read the cell polarity axis and how spindle attachment is coupled to mitotic progression remains poorly understood. We explore these questions in Drosophila sensory organ precursors (SOPs), which divide asymmetrically to give rise to epidermal mechanosensory bristles. We show that the scaffold protein Meru, which is enriched at the posterior cortex by the Frizzled/Dishevelled planar cell polarity complex, in turn recruits Mud, linking the spindle tethering and polarity machineries. Furthermore, Cyclin A/Cdk1 associates with Meru at the posterior cortex, promoting the formation of the Mud/Meru/Dsh complex via Meru and Dsh phosphorylation. Thus, Meru couples spindle orientation with cell polarity and provides a cell cycle-dependent cue for spindle tethering.
正确的有丝分裂纺锤体定向对于组织结构至关重要,并在通过不对称细胞分裂决定细胞命运中发挥重要作用。诸如果蝇Mud(哺乳动物中的NuMA)等纺锤体拴系因子被招募到细胞皮层并捕获星体微管,将纺锤体拉向正确方向。然而,纺锤体拴系复合体如何读取细胞极性轴以及纺锤体附着如何与有丝分裂进程耦合,仍知之甚少。我们在果蝇感觉器官前体细胞(SOPs)中探究这些问题,SOPs通过不对称分裂产生表皮机械感觉刚毛。我们发现支架蛋白Meru,它由卷曲蛋白/无序蛋白平面细胞极性复合体富集于后皮层,进而招募Mud,将纺锤体拴系和极性机制联系起来。此外,细胞周期蛋白A/细胞周期蛋白依赖性激酶1(Cyclin A/Cdk1)在后皮层与Meru结合,通过Meru和无序蛋白(Dsh)磷酸化促进Mud/Meru/Dsh复合体的形成。因此,Meru将纺锤体定向与细胞极性耦合,并为纺锤体拴系提供细胞周期依赖性线索。