Clear communication is a key requirement for successful working relationships and is essential for coordinating the growth and survival of multicellular organisms. Now, Hans-Hermann Gerdes and colleagues have discovered a new type of intercellular communication — tunnelling nanotube (TNT) networks — that could revolutionize our understanding of how cells communicate.

The authors observed TNTs in cultures of rat pheochromocytoma (PC12) cells, using three-dimensional live-cell microscopy. These ultrafine structures are 50–200 nm in diameter, can be up to several cell diameters in length and span the shortest distance between connected cells (see figure). They were also found to contain actin, but not microtubules. Scanning and transmission electron microscopy indicated that TNTs are a continuation of the cell membrane, and further investigation by video microscopy showed that they are produced de novo when filopodia-like projections on one cell make contact with a neighbouring cell. TNTs fail to develop in cells that are treated with a substance that depolymerizes actin, which indicated that the actin-containing projections are essential for TNT formation. But, what exactly do TNTs do?

Image courtesy of Hans-Hermann Gerdes, University of Heidelberg, Germany.

Small vesicular objects were seen moving unidirectionally along TNTs and, using fluorescent dyes, the authors showed that membrane vesicles and organelles, but not small cytoplasmic molecules, could be exchanged between TNT-connected cells. Fluorescently labelled plasma membrane components could selectively flow between TNT-connected cells, indicating that their membranes are continuous. In vivo experiments confirmed that the fluorescently labelled organelles moved unidirectionally through the TNTs, as organelles were observed entering TNTs on one side of a cell–cell connection, moving through the TNT and exiting into the cell on the other side of the TNT.

From these results the authors have proposed a model in which cells form actin-driven projections towards a target cell. Once the projection contacts the target, TNT formation occurs as a result of membrane continuity between the connected cells, and this physical link allows organelles to be unidirectionally transferred to the target cell by an actin-mediated mechanism. As the authors have observed TNTs in other cell lineages, this new long-range form of cell communication probably has an important role in regulating a diverse range of cellular processes.