RRC ID 45779
Author LaBonty M, Szmygiel C, Byrnes LE, Hughes S, Woollard A, Cram EJ.
Title CACN-1/Cactin plays a role in Wnt signaling in C. elegans.
Journal PLoS ONE
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.
Volume 9(7)
Pages e101945
Published 2014
DOI 10.1371/journal.pone.0101945
PII PONE-D-13-14081
PMID 24999833
PMC PMC4084952
MeSH Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Division Cell Proliferation DNA-Binding Proteins / metabolism Gene Expression Regulation, Developmental High Mobility Group Proteins / metabolism Larva / cytology Larva / metabolism Male Membrane Proteins / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Transport Protein-Serine-Threonine Kinases / metabolism RNA Interference Testis / cytology Testis / growth & development Transcription, Genetic Wnt Signaling Pathway* beta Catenin / metabolism
IF 2.766
Times Cited 6
C.elegans tm3042