Journal article
Centrosomal Enrichment and Proteasomal Degradation of SYS-1/β-catenin Requires the Microtubule Motor Dynein
Molecular biology of the cell, Vol.33(5), ar42
02/23/2022
DOI: 10.1091/mbc.E22-02-0031
PMCID: PMC9282011
PMID: 35196020
Abstract
The
Wnt/β-catenin Asymmetry (WβA) pathway utilizes asymmetric regulation of SYS-1/β-catenin and POP-1/TCF coactivators. WβA differentially regulates gene expression during cell fate decisions, specifically by asymmetric localization of determinants in mother cells to produce daughters biased towards their appropriate cell fate. Despite the induction of asymmetry, β-catenin localizes symmetrically to mitotic centrosomes in both mammals and
. Due to the mitosis-specific localization of SYS-1 to centrosomes and enrichment of SYS-1 at kinetochore microtubules when SYS-1 centrosomal loading is disrupted, we investigated active trafficking in SYS-1 centrosomal localization. Here, we demonstrate that trafficking by microtubule motor dynein is required to maintain SYS-1 centrosomal enrichment, by dynein RNAi-mediated decreases in SYS-1 centrosomal enrichment and by temperature-sensitive allele of the dynein heavy chain. Conversely, we observe depletion of microtubules by nocodazole treatment or RNAi of dynein-proteasome adapter ECPS-1 exhibits increased centrosomal enrichment of SYS-1. Moreover, disruptions to SYS-1 or negative regulator microtubule trafficking are sufficient to significantly exacerbate SYS-1 dependent cell fate misspecifications. We propose a model whereby retrograde microtubule-mediated trafficking enables SYS-1 enrichment at centrosomes, enhancing its eventual proteasomal degradation. These studies support the link between centrosomal localization and enhancement of proteasomal degradation, particularly for proteins not generally considered 'centrosomal'.
Details
- Title: Subtitle
- Centrosomal Enrichment and Proteasomal Degradation of SYS-1/β-catenin Requires the Microtubule Motor Dynein
- Creators
- Joshua W Thompson - Department of Biology, University of Iowa, Iowa City, IA 52242-1324Maria F Valdes Michel - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242-1324Bryan T Phillips - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242-1324
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.33(5), ar42
- DOI
- 10.1091/mbc.E22-02-0031
- PMID
- 35196020
- PMCID
- PMC9282011
- NLM abbreviation
- Mol Biol Cell
- eISSN
- 1939-4586
- Language
- English
- Date published
- 02/23/2022
- Academic Unit
- Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984222758702771
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