The tumor suppressor APC differentially regulates multiple β-catenins through the function of axin and CKIα during C. elegans asymmetric stem cell divisions.

Abstract

The APC tumor suppressor regulates diverse stem cell processes including gene regulation through Wnt-β-catenin signaling and chromosome stability through microtubule interactions, but how the disparate functions of APC are controlled is not well understood. Acting as part of a Wnt-β-catenin pathway that controls asymmetric cell division, Caenorhabditis elegans APC, APR-1, promotes asymmetric nuclear export of the β-catenin WRM-1 by asymmetrically stabilizing microtubules. Wnt function also depends on a second β-catenin, SYS-1, which binds to the C. elegans TCF POP-1 to activate gene expression. Here, we show that APR-1 regulates SYS-1 levels in asymmetric stem cell division, in addition to its known role in lowering nuclear levels of WRM-1. We demonstrate that SYS-1 is also negatively regulated by the C. elegans homolog of casein kinase 1α (CKIα), KIN-19. We show that KIN-19 restricts APR-1 localization, thereby regulating nuclear WRM-1. Finally, the polarity of APR-1 cortical localization is controlled by PRY-1 (C. elegans Axin), such that PRY-1 controls the polarity of both SYS-1 and WRM-1 asymmetries. We propose a model whereby Wnt signaling, through CKIα, regulates the function of two distinct pools of APC - one APC pool negatively regulates SYS-1, whereas the second pool stabilizes microtubules and promotes WRM-1 nuclear export.

• Authors: Austin T Baldwin, Bryan T Phillips
• Journal: Journal of cell science (J Cell Sci) Vol. 127 Issue Pt 12 Pg. 2771-81 (Jun 15 2014) ISSN: 1477-9137 [Electronic] England
• PMID: 24762815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014. Published by The Company of Biologists Ltd.

Chemical References

• Adenomatous Polyposis Coli Protein
• Caenorhabditis elegans Proteins
• Cytoskeletal Proteins
• Pry-1 protein, C elegans
• Sys-1 protein, C elegans
• Transcription Factors
• WRM-1 protein, C elegans
• Protein Kinases
• KIN-19 protein, C elegans

Topics

• Active Transport, Cell Nucleus
• Adenomatous Polyposis Coli Protein (physiology)
• Animals
• Asymmetric Cell Division
• Caenorhabditis elegans (cytology, genetics, metabolism)
• Caenorhabditis elegans Proteins (genetics, metabolism, physiology)
• Cell Nucleus (physiology)
• Cell Polarity
• Cytoskeletal Proteins (genetics, metabolism)
• Microtubules (metabolism)
• Protein Kinases (metabolism)
• Protein Transport
• Stem Cells (physiology)
• Transcription Factors (genetics, metabolism)
• Wnt Signaling Pathway