Long-distance relationships: do membrane nanotubes regulate cell–cell communication and disease progression?

Metazoan cells rapidly exchange signals at tight cell-cell interfaces, including synapses and gap junctions. Advances in imaging recently exposed a third mode of intercellular cross-talk mediated by thin, actin-containing membrane extensions broadly known as "membrane" or "tunneling" nanotubes. An explosion of research suggests diverse functions for nanotubular superhighways, including cell-cell electrical coupling, calcium signaling, small-molecule exchange, and, remarkably, the transfer of bulky cargoes, including organelles or pathogenic agents. Despite great enthusiasm for all things nanotubular and their potential roles in cell signaling and pathogenesis, key questions remain regarding the mechanisms by which these structures regulate directional cell-cell exchange; how these linkages are formed and between which cells and, critically, whether nanotubes are as prevalent in vivo as they appear to be in the incubator.