title: Unique and redundant β-catenin regulatory roles of two Dishevelled paralogs during C. elegans asymmetric cell division.
abstract: The Wnt/β-catenin signaling pathway is utilized across metazoans. However, the mechanism of signal transduction, especially dissociation of the β-catenin destruction complex by Dishevelled proteins, remains controversial. Here, we describe the function of the Dishevelled paralogs DSH-2 and MIG-5 in the Wnt/β-catenin asymmetry (WβA) pathway in Caenorhabditis elegans, where WβA drives asymmetric cell divisions throughout development. We find that DSH-2 and MIG-5 redundantly regulate cell fate in hypodermal seam cells. Similarly, both DSH-2 and MIG-5 are required for positive regulation of SYS-1 (a C. elegans β-catenin), but MIG-5 has a stronger effect on the polarity of SYS-1 localization. We show that MIG-5 controls cortical APR-1 (the C. elegans APC) localization. DSH-2 and MIG-5 both regulate the localization of WRM-1 (another C. elegans β-catenin), acting together as negative regulators of WRM-1 nuclear localization. Finally, we demonstrate that overexpression of DSH-2 or MIG-5 in seam cells leads to stabilization of SYS-1 in the anterior seam daughter, solidifying the Dishevelled proteins as positive regulators of SYS-1. Overall, we have further defined the role of Dishevelled in the WβA signaling pathway, and demonstrated that DSH-2 and MIG-5 regulate cell fate, β-catenin nuclear levels and the polarity of β-catenin regulation.
authors.affiliation: Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA.
authors.forename: Austin T
authors.initials: AT
authors.lastname: Baldwin
authors.affiliation: Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Clemons
authors.affiliation: Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242-1324, USA bryan-phillips@uiowa.edu.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Phillips
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000072261:Dishevelled Proteins / Q000502:physiology*; D055550:Protein Stability; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; C515316:Mig-5 protein, C elegans; C117260:Pry-1 protein, C elegans; C502083:Sys-1 protein, C elegans; D014157:Transcription Factors; C120104:WRM-1 protein, C elegans; D051176:beta Catenin; C505142:dsh-2 protein, C elegans
keywords: APC; Asymmetric Cell Division; Dishevelled; Wnt; β-Catenin