Cells of the C. elegans embryo navigate through invariant lineages in serial asymmetric cell divisions (ACDs), many of which are controlled by a modified Wnt/β-catenin signaling strategy. Daughter cells derived from a Wnt-dependent ACD exhibit nuclear asymmetry of the transcriptional coactivator SYS-1/β-catenin, resulting in differential activation of Wnt-responsive target genes and distinct cell fates. We investigated how dynamic localization of SYS-1 to mitotic centrosomes influenced SYS-1 inheritance and cell fate outcomes in daughter cells after division of the endomesodermal (EMS) blastomere. Through yeast two-hybrid screening, we identified the centrosomal protein RSA-2 as a SYS-1 binding partner and showed that localization of SYS-1 to mitotic centrosomes was dependent on RSA-2. Uncoupling SYS-1 from the centrosome by RSA-2 depletion increased SYS-1 inheritance after ACD and promoted Wnt-dependent cell fate. Photobleaching experiments revealed that the entire fraction of centrosome-bound SYS-1 turns over rapidly during mitosis. Interestingly, disruption of the proteasome led to an increased accumulation of SYS-1 at the centrosome but decreased the mobile fraction and turnover rate. 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. These results suggest that proper spatial organization of signaling effectors such as SYS-1/β-catenin is necessary for permitting their efficient regulation during dynamic processes such as ACD. .
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