Dictyostelium discoideum is a social amoeba: a single-celled organism that can group together to form a multicellular slug. Although it has mostly been used as an experimental model for studying chemotaxis, cell-cell communication, and the evolution of sociality, some researchers are using it as a window into how multicellular life could have evolved. Now, Daniel Dickinson, a graduate student at Stanford University, has discovered that the Dictyostelium slug does more than simply take on a multicellular form; it also creates a tissue that has only ever been seen before in animals.
When Dickinson became a student of William Weis and James Nelson, who collaborate to study the adhesion protein a-catenin—a membrane protein necessary for forming epithelial tissues in animals—he wanted to explore how a-catenin had changed throughout evolution. He searched for a-catenin in sequence databases, and to his surprise, found the protein expressed in Dictyostelium. This protein “had no business being present in any organism outside of animals,” says Dickinson, so he set out to find out what it was doing there.
Dickinson cloned a-catenin and raised antibodies against the protein. He ran Western blots of Dictyostelium at different stages in its life cycle, and found that a-catenin was only expressed in the multicellular stage. After experimenting with different ways of fixing and staining the cells, he found the protein localized to the cell-cell contacts in a single layer of cells at the tip of the fruiting body. Intriguingly, this layer of cells was polarized, arranging its Golgi, centrosomes, and proteins at either the top or the bottom of the cell—the first instance of polarized epithelial cells reported in Dictyostelium.
In animals, a-catenin creates a sticky junction between cells by binding to another adhesion protein, ß-catenin. Dictyostelium also has a ß-catenin-related protein, called Aardvark. When Dickinson knocked down a-catenin using siRNA, the cells lost polarity. In addition, the epithelial monolayer and the slug’s stalk didn’t form. Knocking out the Aardvark gene had a similar but less severe effect, showing that both catenins work together to support cell polarization and epithelium formation.
Stable polarization, says Helen Skaer of the University of Cambridge, “is characteristic of multicellular organisms,” and depends on several different proteins and interactions. Remarkably, polarization in Dictyostelium appears to depend on these two proteins, “which is not what you’d expect from looking at more complex multicellular organisms,” says Skaer. Finding a-catenin with a bona fide multicellular function in such an evolutionarily primitive organism “blows my mind,” says Dickinson.
There is one missing part to the puzzle, however. In animals, a-catenin is connected to the membrane by a protein of the cadherin family. Dickinson hasn’t been able to find a Dictyostelium cadherin homolog. “There’s a big hole in the molecular mechanism,” he says. It’s a problem he intends to study further in order to better understand the evolution of cell-cell adhesions and the formation of more complicated tissue structures.