The art of cellular communication: tunneling nanotubes bridge the divide

Abstract

The ability of cells to receive, process, and respond to information is essential for a variety of biological processes. This is true for the simplest single cell entity as it is for the highly specialized cells of multicellular organisms. In the latter, most cells do not exist as independent units, but are organized into specialized tissues. Within these functional assemblies, cells communicate with each other in diVerent ways to coordinate physiological processes. Recently, a new type of cell-to-cell communication was discovered, based on de novo formation of membranous nanotubes between cells. These F-actin-rich structures, referred to as tunneling nanotubes (TNT), were shown to mediate membrane continuity between connected cells and facilitate the intercellular transport of various cellular components. The subsequent identiWcation of TNTlike structures in numerous cell types revealed some structural diversity. At the same time it emerged that the direct transfer of cargo between cells is a common functional property, suggesting a general role of TNT-like structures in selective, long-range cell-to-cell communication. Due to the growing number of documented thin and long cell protrusions in tissue implicated in cell-to-cell signaling, it is intriguing to speculate that TNT-like structures also exist in vivo and participate in important physiological processes.

Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks

“…They were identified in a variety of cultured cell systems, including cells of the immune system, kidney cells, PC12 cells and cells from human glioblastoma (figure 4 and table 2) [13,32,33,101,102]. TNTs have a diameter of 50-200 nm and a length up to several cell diameters.…”

“…Cargo transfer of endosome-derived vesicles and membrane-anchored proteins takes place. The mechanism involves a unidirectional vesicle transfer which is based on actin action [101]. It seems possible that membrane receptors can move via TNTs from the plasma membrane of one cell to the plasma membrane of another cell [53].…”

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

“…The connecting structures, called nanotubes, can bridge distances of more than 100 μm, depending on the cell type [48,49]. They are versatile in ultra-structure and formation, and consequently also in function [reviewed in [50][51][52][53]. Our recent results revealed that the nanotubes in epithelial cells can be divided into two distinct types with respect to their formation, stability and cytoskeletal content [9].…”

Generation of phospholipid vesicle-nanotube networks and transport of molecules therein

“…Intercellular nanotubes (ICNs) formed from filopodial structures or after separation of tight cell-cell contacts mediate transport processes between cells. For example, diffusion of inositol triphosphate through nanotubes possibly mediates calcium signaling between macrophages, a gradient of membrane tension can induce transport of membrane patches and surface proteins, and molecular motors can transport organelles along filamentous actin in ICNs [5][6][7] . Land plants have developed plasmodesmata, a form of sophisticated membrane channel used to span the rigid cell walls to mediate the cell-to-cell exchange of signaling molecules 8 .…”