Wiring through tunneling nanotubes - from electrical signals to organelle transfer

Tunneling nanotubes (TNTs) represent a subset of F-actin-based transient tubular connections that allow direct communication between distant cells. Recent studies have provided new insights into the existence of TNTs in vivo, and this novel mechanism of intercellular communication is implicated in various essential processes, such as development, immunity, tissue regeneration and transmission of electrical signals. TNTs are versatile structures known to facilitate the transfer of various cargos, such as organelles, plasma membrane components, pathogens and Ca2+. Recently, a new function of TNTs in the long-range transfer of electrical signals that involves gap junctions has been suggested. This indicates that different types of TNTs might exist, and supports the notion that TNTs might not be just passive open conduits but rather are regulated by gating mechanisms. Furthermore, TNTs have been found in different cell lines and are characterized by their diversity in terms of morphology. Here we discuss these novel findings in the context of the two models that have been proposed for TNT formation, and focus on putative proteins that could represent TNT specific markers. We also shed some light on the molecular mechanisms used by TNTs to transfer cargos, as well as chemical and electrical signals.