A mechanism important during asymmetric cell division in development is the polarized trafficking of endosomes, as this leads to differential levels of critical signaling proteins that control cell fate. Recently, Planelles-Herrero et al. identified a critical protein complex known as Elongator which is essential to control spindle asymmetry through the regulation of microtubules. The group utilized microscopy techniques to show that depletion of the Elongator complex via RNAi led to the loss of spindle asymmetry in sensory organ precursor cells (SOPs) from Drosophila melanogaster. Furthermore, in the same model depletion of Elongator also diminished polarized trafficking of endosomes containing the Notch ligand Delta, a key regulator of cell fate. To Define the mechanism by which Elongator controls this critical mechanism they performed critical in vitro co-sedimentation studies to show that Elongator can directly bind to microtubules. This was confirmed via TIRF studies, and importantly it was shown that the whole complex was needed for effective binding to microtubules. Specific point mutations of the subunit Elp3 of the Elongator complex were used to test whether established acetylase and methylase function, important for transfer-RNA synthesis, was needed for regulation of spindle symmetry; surprisingly, it had no role in this newly discovered function of the Elongator complex. Rather, Elongator was shown to directly alter microtubule dynamics both through enhanced growth speed and stability. Finally, the group showed that altering Elongator localization was sufficient to suppress microtubule levels in the spindle which blunted polarization of Delta-containing endosomes. Cytoskeleton Inc’s purified (Cat. #T240) and fluorescently labeled tubulins (Cat. #TL590M, TL670M) were essential for many of the in vitro studies used to define Elongator’s effects on microtubules.
Above: Schematic on how loss of Elongator complex alters spindle asymmetry and asymmetric cell division
Link to Citation:
Planelles-Herrero VJ. et al. Elongator stabilizes microtubules to control central spindle asymmetry and polarized trafficking of cell fate determinants. Nat Cell Biol. 2022 Nov;24(11):1606-1616. doi: 10.1038/s41556-022-01020-9.
Related Products/Products Used