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

Setu Vora; Bryan T Phillips

doi:10.1016/j.cub.2015.02.020

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

Journal article

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

Setu Vora and Bryan T Phillips

Current biology, Vol.25(8), pp.1005-1016

04/20/2015

DOI: 10.1016/j.cub.2015.02.020

PMID: 25819561

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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.

Transcription Factors - metabolism

Asymmetric Cell Division - genetics

Animals

Caenorhabditis elegans - cytology

Proteolysis

Caenorhabditis elegans Proteins - metabolism

Signal Transduction - genetics

Proteasome Endopeptidase Complex - metabolism

Wnt Proteins - metabolism

beta Catenin - metabolism

Asymmetric Cell Division - physiology

Centrosome - metabolism

Details

Title: Subtitle: Centrosome-Associated Degradation Limits β-Catenin Inheritance by Daughter Cells after Asymmetric Division
Creators: Setu Vora - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Bryan T Phillips - Department of Biology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: bryan-phillips@uiowa.edu
Resource Type: Journal article
Publication Details: Current biology, Vol.25(8), pp.1005-1016
DOI: 10.1016/j.cub.2015.02.020
PMID: 25819561
NLM abbreviation: Curr Biol
ISSN: 0960-9822
eISSN: 1879-0445
Grant note: P40 OD01440 / NIH HHS
Language: English
Date published: 04/20/2015
Academic Unit: Biology
Record Identifier: 9984083998002771

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