Nanotubes enable intercellular communication in early-branching eukaryotes

Social amoebae, despite being unicellular organisms, exhibit multicellular phenotypes that require well-tuned inter- and intracellular communication modes. The social amoeba Dictyostelium discoideum is an excellent model to study multicellularity and metazoan cell signaling. While communication based on secreted small molecules has been described, juxtacrine connections were so far an unexplored intercellular communication mechanism in amoebae. Using fluorescence labeling and confocal microscopy, we identified de novo formation of tunneling nanotubes (TNTs) in amoebae. Live cell imaging revealed that these nanotubes are actin-rich protrusions that facilitate cargo transport by enabling membrane continuity between the connected cells. The identification of nanotubes in different amoebal species highlights the relevance of these protrusions within natural microbial communities since they act as a complementary mechanism for the transfer of essential cellular cargo. Remarkably, TNT-mediated connectivity persists under conditions that perturb cytoskeletal dynamics, indicating that nanotube-based communication is robust and adaptable. TNTs represent a novel juxtacrine communication machinery that promotes cell-to-cell communication and coordination in early eukaryotes and could play a key role in the emergence of multicellularity.