The Divergent Caenorhabditis elegans β-Catenin Proteins BAR-1, WRM-1 and HMP-2 Make Distinct Protein Interactions but Retain Functional Redundancy in Vivo

Abstract

β-Catenins function both in cell adhesion as part of the cadherin/catenin complex and in Wnt signal transduction as transcription factors. Vertebrates express two related proteins, β-catenin and plakoglobin, while Drosophila has a single family member, Armadillo. Caenorhabditis elegans expresses three β-catenin-related proteins, BAR-1, HMP-2, and WRM-1, which are quite diverged in sequence from each other and other β-catenins. While BAR-1 and WRM-1 are known to act in Wnt-mediated processes, and HMP-2 acts in a complex with cadherin/α-catenin homologs, it is unclear whether all three proteins retain the other functions of β-catenin. Here we show that BAR-1, like vertebrate β-catenin, has redundant transcription activation domains in its amino- and carboxyl-terminal regions but that HMP-2 and WRM-1 also possess the ability to activate transcription. We show via yeast two-hybrid analysis that these three proteins display distinct patterns of protein interactions. Surprisingly, we find that both WRM-1 and HMP-2 can substitute for BAR-1 in C. elegans when expressed from the bar-1 promoter. Therefore, although their mutant phenotypes and protein interaction patterns strongly suggest that the functions of β-catenin in other species have been segregated among three diverged proteins in C. elegans, these proteins still retain sufficient similarity to display functional redundancy in vivo.

Walking the tight wire between cell adhesion and WNT signalling: a balancing act for β-catenin

“…Whether the transcriptional or adhesive functions arose first, or perhaps simultaneously, remains unknown [65][66][67]. The two functions can be separated, as evidenced by the existence of multiple CTNNB1 homologues in Caenorhabditis elegans, some of which are exclusively involved in transcription or adhesion [68][69][70]. On a final note, a CTNNB1/CTNNA1 module regulates polarization of a simple epithelium in the slime mold Dictyostelium discoideum at a transient, multicellular life stage [71].…”