CACN-1/Cactin plays a role in Wnt signaling in C. elegans

• Published in: PloS one 2014-07, Vol.9 (7), p.e101945-e101945
• Main Authors: LaBonty, Melissa, Szmygiel, Cleo, Byrnes, Lauren E, Hughes, Samantha, Woollard, Alison, Cram, Erin J
• Format: Article
• Language: English
• Subjects: Animals; Asymmetry; beta Catenin - metabolism; Biochemistry; Biology; Biology and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cancer; Cell cycle; Cell Division; Cell number; Cell Proliferation; Daughters; Depletion; DNA-Binding Proteins - metabolism; Drosophila; Embryos; Gene expression; Gene Expression Regulation, Developmental; Heparan sulfate; High Mobility Group Proteins - metabolism; Insects; Kinases; Larva - cytology; Larva - metabolism; Larval development; LEF protein; Localization; Male; Membrane Proteins - metabolism; Morphogenesis; Nematodes; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclei; Pathways; Protein Serine-Threonine Kinases - metabolism; Protein Transport; Proteins; Research and Analysis Methods; RNA Interference; RNA-mediated interference; Signal transduction; Signaling; Testis - cytology; Testis - growth & development; Transcription activation; Transcription factors; Transcription, Genetic; Uterus; Wnt protein; Wnt Signaling Pathway; Worms; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101945

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.