The Elongator complex controls symmetry breaking of the central spindle and thereby polarized trafficking of cell fate determinants during asymmetric cell division

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• Vicente Jose Planelles Herrero – Derivery group – MRC LMB
• Wednesday 26 February 2020, 17:30-19:30
• Gurdon Institute Tea Room.

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Asymmetric cell division gives rise to two daughter cells that inherit different determinants, thereby acquiring different fates. The polarized sorting of signalling endosomes from an asymmetric central spindle has emerged as an important feature of asymmetric cell division in Drosophila Sensory Organ Precursors (SOP). However, how symmetry breaking of the central spindle occurs in vivo remains poorly understood. Here, we have identified the Elongator complex as a new player in this pathway. Elongator is a multiprotein complex involved in the regulation of transcription and translation through histone acetylation and tRNA methylation, respectively. We found that, in SOPs, Elongator localizes to the central spindle, and that deletion of the catalytical subunit Elp3 abolishes central spindle asymmetry and, accordingly, Sara endosome asymmetric segregation. As Sara endosomes contain the cell fate determinants Notch and Delta, this induces cell fate phenotypes in the adult fly. We further investigated the molecular mechanism by which Elongator breaks the symmetry of the central spindle. Mammalian Elongator has previously been proposed to acetylate microtubules, potentially controlling their dynamics. However, we found that Drosophila Elongator does not acetylate tubulin and that Elp3 mutants can be rescued with an acetylase-dead version of Elp3 in vivo. Rather, we found that Elongator binds to microtubules, lowering their frequency of catastrophe in in vitro single molecule assays, suggesting that Elongator asymmetrically stabilizes microtubules on one side of the central spindle, thereby generating central spindle asymmetry. We demonstrate this by modifying the Elongator activity gradient through asymmetric targeting of Elongator to the anterior cortex, perturbing Sara endosome asymmetric segregation. Altogether, our data suggests that Elongator constitutes a novel link between polarity cues at the cell cortex and symmetry breaking of the microtubule cytoskeleton.

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