title: Centrosome-Associated Degradation Limits β-Catenin Inheritance by Daughter Cells after Asymmetric Division.
abstract: 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.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Setu
authors.initials: S
authors.lastname: Vora
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: bryan-phillips@uiowa.edu.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Phillips
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C502083:Sys-1 protein, C elegans; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D046988:Proteasome Endopeptidase Complex