CACN-1/Cactin Plays a Role in Wnt Signaling in C-elegans

被引:14
作者
LaBonty, Melissa [1 ]
Szmygiel, Cleo [1 ]
Byrnes, Lauren E. [1 ]
Hughes, Samantha [2 ]
Woollard, Alison [2 ]
Cram, Erin J. [1 ]
机构
[1] Northeastern Univ, Dept Biol, Boston, MA 02115 USA
[2] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
来源
PLOS ONE | 2014年 / 9卷 / 07期
基金
美国国家卫生研究院;
关键词
ASYMMETRIC CELL-DIVISION; BETA-CATENIN; RECIPROCAL ASYMMETRY; GENE-EXPRESSION; AXIS FORMATION; SEAM CELLS; KAPPA-B; PROTEIN; POP-1; CACTIN;
D O I
10.1371/journal.pone.0101945
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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/b-catenin or Wnt/b-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/b-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.
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页数:15
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