Centrosome-Associated Degradation Limits β-Catenin Inheritance by Daughter Cells after Asymmetric Division

Caenorhabditis elegans embryos rapidly diversify cell fate using a modified Wnt/β-catenin signaling strategy to carry out serial asymmetric cell divisions (ACDs). Wnt-dependent ACDs rely on nuclear asymmetry of the transcriptional coactivator SYS-1/β-catenin between daughter cells to differentially activate Wnt-responsive target genes. Here, we investigate how dynamic localization of SYS-1 to mitotic centrosomes influences SYS-1 inheritance in daughter cells and cell-fate outcomes after ACD. Through yeast two-hybrid screening, we identify the centrosomal protein RSA-2 as a SYS-1 binding partner and show that localization of SYS-1 to mitotic centrosomes is dependent on RSA-2. Uncoupling SYS-1 from the centrosome by RSA-2 depletion increases SYS-1 inheritance after ACD and promotes Wnt-dependent cell fate. Photobleaching experiments reveal that centrosome-bound SYS-1 turns over rapidly. Interestingly, disruption of the proteasome leads to an increased accumulation of SYS-1 at the centrosome but disrupts its dynamic turnover. We conclude that centrosomal targeting of SYS-1 promotes its degradation during asymmetric cell division. We propose a model whereby centrosome-associated SYS-1 degradation couples negative regulation with cell-division timing to facilitate SYS-1 clearance from the mother cell at the time of asymmetric division. Based on our observations of centrosomal SYS-1 dynamics, we discuss the possibility that the centrosome may coordinate various cell-cycle-dependent processes by synchronizing mitosis and protein regulation. •SYS-1/β-catenin localizes to centrosomes during C. elegans asymmetric cell division•Targeting of SYS-1 to centrosomes depends on the centrosomal protein RSA-2•Depletion of RSA-2 leads to increased SYS-1 retention in daughter cells•Loss of the proteasome leads to decreased turnover of centrosomal SYS-1 Wnt/β-catenin signaling controls development in many animals and specifically drives serial asymmetric cell divisions during C. elegans embryogenesis. Vora and Phillips show that targeting of SYS-1/β-catenin to mitotic centrosomes promotes its degradation during division, thus limiting its inheritance by daughter cells.