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.

TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin

“…It has been reported that [31][32][33]28]. Human Cactin has been reported to interact with IκBL, which is one of negative regulators of the NFκB signaling pathway [27].…”

Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion

“…Human cactin was later found to physically and functionally interact with IκB-like protein (IκBL) and to be part of a negative feedback loop that controls NFκB transcriptional response (Suzuki et al, 2016), suggesting a conserved function for cactins in immune response and development (Atzei et al, 2010a). To date, cactin orthologs have been studied also in Toxoplasma gondii, Litopenaeus vannamei, Arabidopsis thaliana, Caenorhabditis elegans, and Danio rerio (Atzei et al, 2010b;Baldwin et al, 2013;Cecchetelli et al, 2016;Doherty et al, 2014;LaBonty et al, 2014;Szatanek et al, 2012;Tannoury et al, 2010;Zhang et al, 2014). In these organisms, cactin loss-of-function is associated with compromised cell viability and proliferation, and with developmental defects, highlighting the essentiality of cactin proteins.…”

Follicle populations and gene expression profiles of Nelore and Angus heifers with low and high ovarian follicle counts

“…These genes have been associated with cell proliferation in ovarian cancer and mitosis of ovarian germ cells. Downregulation of CACNA1 in somatic gonad cells through RNA interference (RNA i ) leads to an increase in POP1 expression, which negatively regulates cell proliferation (LaBonty et al, ). Basic FGF ( bFGF ) plays diverse roles in cell proliferation and differentiation during embryo development.…”