UC Berkeley

The question of how animals evolved from a unicellular ancestor has challenged evolutionary biologists for decades. Because cell adhesion and signaling are required for multicellularity, understanding how these cellular processes evolved will provide key insights into the origin of animals. A critical finding is that choanoflagellates, the closest living unicellular relatives of animals, express members of the cadherin superfamily. Cadherins are pivotal for animal cell adhesion and signaling and were previously thought to be unique to animals, making them crucial to understanding the evolutionary origin and transition to multicellularity. Importantly, the presence of cadherins in choanoflagellates allows a consideration of their ancestral function in the unicellular progenitor of animals. To gain insight into the ancestral structure and function of cadherins, I reconstructed the domain content of cadherins from the last common ancestor of choanoflagellates and metazoans. Conservation of diverse protein domains in the choanoflagellate Monosiga brevicollis and metazoan cadherins suggests that ancestral cadherins served both signaling and adhesive functions. I find that two M. brevicollis cadherin containing an ancestral domain combination MBCDH1 and a close paralog, MBCDH2, localize to the actin-filled microvilli of the feeding collar. Interestingly, the protein abundance of these cadherins changes in response to bacterial food availability. In vitro studies, as well as experiments performed in a heterologous cell culture system, suggest that MBCDH1 does not mediate homophilic adhesion in the context of these experiments like some metazoan cadherins and thus may play a role in cell signaling. Taken together, these data suggest that cadherins may mediate interactions with the extracellular environment, including the recognition and capture of bacterial prey. I hypothesize that metazoan cadherins were co-opted to mediate cell-cell interactions from ancestral proteins that interpreted and responded to extracellular cues.