Tunneling nanotubes: emerging view of their molecular components and formation mechanisms

Cell-to-cell communication is essential for the development and maintenance of multicellular organisms. The tunneling nanotube (TNT) is a recently recognized distinct type of intercellular communication device. TNTs are thin protrusions of the plasma membrane and allow direct physical connections of the plasma membranes between remote cells. The proposed functions for TNTs include the cell-to-cell transfer of large cellular structures such as membrane vesicles and organelles, as well as signal transduction molecules in a wide variety of cell types. Moreover TNT and TNT-related structures are thought to facilitate the intercellular spreading of virus and/or pathogenic proteins. Despite their contribution to normal cellular functions and importance in pathological conditions, virtually nothing is known about the molecular basis for their formation. We have recently shown that M-Sec (also called TNFaip2) is a key molecule for TNT formation. In cooperation with the RalA small GTPase and the exocyst complex, M-Sec can induce the formation of functional TNTs, indicating that the remodeling of the actin cytoskeleton and vesicle trafficking are involved in M-Sec-mediated TNT formation. Discovery of the role of M-Sec will accelerate our understanding of TNTs, both at the molecular and physiological levels.