title: CACN-1/Cactin plays a role in Wnt signaling in C. elegans.
abstract: Wnt signaling is tightly regulated during animal development and controls cell proliferation and differentiation. In C. elegans, activation of Wnt signaling alters the activity of the TCF/LEF transcription factor, POP-1, through activation of the Wnt/β-catenin or Wnt/β-catenin asymmetry pathways. In this study, we have identified CACN-1 as a potential regulator of POP-1 in C. elegans larval development. CACN-1/Cactin is a well-conserved protein of unknown molecular function previously implicated in the regulation of several developmental signaling pathways. Here we have used activation of POPTOP, a POP-1-responsive reporter construct, as a proxy for Wnt signaling. POPTOP requires POP-1 and SYS-1/β-catenin for activation in L4 uterine cells. RNAi depletion experiments show that CACN-1 is needed to prevent excessive activation of POPTOP and for proper levels and/or localization of POP-1. Surprisingly, high POPTOP expression correlates with increased levels of POP-1 in uterine nuclei, suggesting POPTOP may not mirror endogenous gene expression in all respects. Genetic interaction studies suggest that CACN-1 may act partially through LIT-1/NLK to alter POP-1 localization and POPTOP activation. Additionally, CACN-1 is required for proper proliferation of larval seam cells. Depletion of CACN-1 results in a loss of POP-1 asymmetry and reduction of terminal seam cell number, suggesting an adoption of the anterior, differentiated fate by the posterior daughter cells. These findings suggest CACN-1/Cactin modulates Wnt signaling during larval development.
authors.affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: LaBonty
authors.affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Cleo
authors.initials: C
authors.lastname: Szmygiel
authors.affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Byrnes
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hughes
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Woollard
authors.affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Cram
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D013737:Testis / Q000166:cytology / Q000254:growth & development; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000595442:CACN-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051176:beta Catenin; C096787:pop-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C120085:lit-1 protein, C elegans