A cell extends a threadlike tube to a neighbor, attaches, and transfers a small organelle from one cell to the other. Such a scenario describes a newly discovered type of cell-to-cell communication [Science, 303, 1007 (2004)].
“The discovery is spectacular,” says Owe Orwar, professor of biophysical chemistry at Chalmers University of Technology, Göteborg, Sweden. Orwar has helped develop artificial systems that demonstrate similar transport (C&EN, May 19, 2003, page 14).
No one, however, has previously observed such behavior in a natural system, says Hans-Hermann Gerdes, lead author of the study, professor of biomedicine at the University of Bergen, Norway, and professor of neurobiology at the University of Heidelberg, Germany. The narrow tubes, or what the researchers call “tunneling nanotubes” (TNTs), are extremely delicate. Just changing the media in a culture plate can destroy them. Moreover, cells often have a mass of stringlike protrusions extending outward. Catching the right microscopic view where one tube attaches to two cells in the same plane is unusual. Graduate student Amin Rustom first spotted the tubes in live, cultured rat cells and followed up to fully characterize the structures.
Each tube consists of an outer phospholipid layer continuous with each cell’s plasma membrane and an inner core made up of the protein actin.
The thin tubes can be quite long for their delicacy—up to several cell diameters. Tube diameters range from 50 to 200 nm. The tubes are taut and are often found between cells that are moving apart, as if the tubes form when cells are near and extend as the cells diverge. But tubes also form between cells that are already some distance apart. Gerdes and colleagues watched as one cell sent out multiple arms (filopodia) in the direction of the target cell. Once one arm connected, which took about four minutes, the other filopodia disappeared.
Small molecules and cell cytoplasm are blocked from traveling through the tubes. Gerdes suspects that the actin core essentially plugs each tube, and only organelles that become associated with the actin core move through the tube.
The European researchers watched endosomes—small organelles that form by budding off the plasma membrane—travel through the tubes, moving at a speed of about 25 nm per second and in one direction only. (Plasma membrane proteins also travel from cell to cell on the outside of the tube because of the continuous plasma membrane.)
There are faster forms of cellular communication. But a slower, long-range organelle transfer may play a crucial role in development and maintenance of multicellular organisms, Gerdes says. TNTs may fit the description of known cell-to-cell communication scenarios, he says. For example, argosomes, which are endosome-like organelles, transfer differentiation signals to developing cells, but it has been difficult to explain the long-range communication known to occur. Gerdes suggests that other signals, including apoptosis and immunogenic signals, may also be relayed through TNTs.
“My opinion,” says Thomas B. Kornberg, professor of biochemistry and biophysics at the University of California, San Francisco, “is that this phenomenon is widespread and it is significant. Having said that, I think it is important to temper any conclusions that are based on the behavior of cells in culture.”
Finding out whether TNTs play a significant role in tissue will be harder, Gerdes says. The dense packing of tissue cells makes it difficult to see between them.
“This phenomenon is widespread and it is significant. Having said that, I think it is important to temper any conclusions that are based on the behavior of cells in culture.”
Thomas Kornberg, University of California, San Francisco