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

• DOI: 10.1016/j.cub.2015.02.020
• Publication Date: 2015-04-20T15:46:37Z
• Authors: Setu Vora; Bryan T. Phillips
• Keywords: Centrosome cycle; Asymmetric cell division; Cell fate determination; Nocodazole

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.