Evidence for an Early Cadherin–Catenin Interaction Network in Ctenophores

Abstract The Cadherin-Catenin Complex (CCC) is a calcium-dependent assembly that is essential for the organization and function of animal cells and tissues. CCC components form adherens junctions that link cell adhesion to the actin cytoskeleton and important signaling pathways that control processes like gene expression, cell polarity, and growth. While the CCC has been extensively studied and known to be conserved across most metazoan lineages, its occurrence in ctenophores, one of the earliest branching groups, has been questioned, with implications for the origins of multicellularity in animals. Here, we show that the ctenophore Mnemiopsis leidyi possesses a reduced cadherin repertoire yet retains conserved interactions characteristic of the CCC. Phylogenetic analyses identified a novel ctenophore-specific cadherin phylogenetically distant from major cadherin families from other animals. Screening a custom yeast 2-hybrid library, derived from M. leidyi embryo cDNA, with the cytoplasmic tail of this non-canonical cadherin-like protein identified known CCC components β-catenin, p120, and Hakai as interacting proteins. Similarly, a screen using M. leidyi α-catenin as bait identified β-catenin, vinculin, and other known actin cytoskeleton-associated proteins. Directed yeast 2-hybrid assays confirmed key interactions and demonstrated that targeted mutagenesis of conserved residues abolished binding, as is observed in other metazoans. Together, these findings suggest that core molecular interactions underlying the CCC are conserved in M. leidyi, consistent with the hypothesis that a functional CCC was an ancestral trait foundational to the evolution of multicellular animals.