By Amy Maxmen

Researchers have discovered a means of cell communication that may illuminate events ranging from embryo development to brain activity.

A Norway-based team reported in the September 20 issue of Proceedings of the National Academy of Sciences that electrical signals can be transmitted between distant cells by means of nanotubes--ultrathin cables containing actin proteins--and that "gap junctions" are involved in the process. Gap junctions are proteins that form pores between two adjacent cells, and that can link animal cells directly. Until now, electrical signaling was considered a fast but limited mode of communication, restricted mainly to cells in the heart and brain. But because many types of cells form nanotubes and gap junctions, it seems that electrical communication could be widespread.

"The cells now have telephone cables to talk to each other," says Hans-Hermann Gerdes, a cell biologist at the University of Bergen and a co-author on the paper.

The study suggests that "cells may use electrical communication over long distances and be more interconnected than we thought," says cell biologist Daniel Davis of Imperial College London.

Six years ago, using light microscopy, Gerdes' team discovered the ultrathin cables stretching between kidney cells for distances longer than the diameter of several cells combined. They named them tunneling nanotubes (now also called membrane nanotubes). Various kinds of cells can transport molecules by means of nanotubes in a Petri dish. For example, HIV-1 can travel along nanotubes connecting immune cells, and prions pass through nanotubes connecting neurons. However, ways in which a cell might extrude a nanotube, open the membrane of another cell and insert its cargo were unclear. Furthermore, there was no strong evidence that nanotubes are physiologically relevant, making claims for nanotubes difficult for many scientists to accept.

Bridging the gap

Walther Mothes, a microbiologist at Yale University in New Haven, Conn., has been critical of the nanotube field, but says he is impressed by the current paper because of its demonstration that nanotubes use gap junctions for sending signals. "I think the nanotube field has not been able to explain the phenomenon with existing biological concepts," he explains. "But this report marks the return of the field to plausible cell-biological concepts, which are gap junctions, and that actually makes sense."

Using electrophysiological techniques, the authors show that a current passes down the nanotubes and causes ion channels to open in the membrane of the connecting cell. The resulting influx of ions in turn may modulate pathways involved in processes such as cell movement. But the authors found that if gap junctions were inactivated or absent, the current didn't flow.

This long-distance signaling may account for the coordinated cell migration observed in developing embryos. For example, cells congregate into two folds to form the neural tube, the precursor to the central nervous system, in vertebrate embryos. The cells are obviously communicating in order to synchronize their behavior, says Gerdes, but how they do so has not been clear. Nanotube-mediated electrical signaling provides an alternative to other modes of cell-cell communication that require direct cell contact or soluble secretions.

Gerdes says the findings mean extra layers of communication are present in the human brain, "drastically" increasing the complexity of the system.

"The authors of this paper have identified an exciting way that cells can communicate at a distance. That means you can no longer just think of cells touching each other to coordinate movement," says Michael Levin of Tufts University in Medford, Massachusetts. "Understanding what physiological information these nanotubes pass on will now be a key question for the future."