Journal
CURRENT BIOLOGY
Volume 25, Issue 8, Pages 1005-1016Publisher
CELL PRESS
DOI: 10.1016/j.cub.2015.02.020
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD01440]
- University of Iowa Central Microscopy Research Facility
- Gery Hehman of the Carver Center for Genomics
- American Cancer Society
- Holden Comprehensive Cancer Center [RSG-11-140-01-DC, 77-004-31]
- Roy J. Carver Charitable Trust [13-4131]
- Evelyn Hart Watson fellowship
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Caenorhabditis elegans embryos rapidly diversify cell fate using a modified Wnt/beta-catenin signaling strategy to carry out serial asymmetric cell divisions (ACDs). Wnt-dependent ACDs rely on nuclear asymmetry of the transcriptional coactivator SYS-1/beta-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.
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