Different Types of Cell-to-Cell Connections Mediated by Nanotubular Structures

Abstract

Communication between cells is crucial for proper functioning of multicellular organisms. The recently discovered membranous tubes, named tunneling nanotubes, that directly bridge neighboring cells may offer a very specific and effective way of intercellular communication. Our experiments on RT4 and T24 urothelial cell lines show that nanotubes that bridge neighboring cells can be divided into two types. The nanotubes of type I are shorter and more dynamic than those of type II, and they contain actin filaments. They are formed when cells explore their surroundings to make contact with another cell. The nanotubes of type II are longer and more stable than type I, and they have cytokeratin filaments. They are formed when two already connected cells start to move apart. On the nanotubes of both types, small vesicles were found as an integral part of the nanotubes (that is, dilatations of the nanotubes). The dilatations of type II nanotubes do not move along the nanotubes, whereas the nanotubes of type I frequently have dilatations (gondolas) that move along the nanotubes in both directions. A possible model of formation and mechanical stability of nanotubes that bridge two neighboring cells is discussed.

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

“…The results of some recent studies indicate that in many cases, vesicular transport between cells and between cell organelles over longer distances is not random, and that it takes place between specific surface regions of the cell organelles [6][7][8][9]. Such organized transport may be achieved via nanotubedirected transport involving carrier vesicles, or via direct transport through nanotubes.…”

“…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]. Type I nanotubes are shorter, usually not longer than 30 μm, are more dynamic, and contain actin filaments.…”

“…The main subject of this review is cell-to-cell communication mediated by the transport of microvesicles [1][2][3][4] that are free to travel to distal cells and fuse with them [5] or by nanotubes that connect neighboring cells [6][7][8][9]. Both microvesicles and nanotubes derive from the cell membrane and are able to transport membrane constituents and the contents of the inner solution.…”

“…An important feature of the formation mechanisms for both is that they are preceeded by lateral reorganization of the membrane into rafts and nanodomains [10][11][12][13][14][15]. As this process is mediated by the local curvature of the membrane, which is in turn determined by the local composition of the constituents, it is the intrinsic shape of the constituents and their interactions with the neighboring molecules [9,11,[15][16][17][18][19][20] that determine whether microvesiculation or tubulation of the membrane occurs [9,10,[13][14][15]. In this review, we present some recent results on the formation of microvesicles and nanotubes, and interpret them in terms of curvature-mediated lateral redistribution of membrane nanodomains.…”

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

“…Nanotubular structures are quite common in biological systems, in particular for establishing cell-to-cell connections 4 . Intercellular nanotubes (ICNs) formed from filopodial structures or after separation of tight cell-cell contacts mediate transport processes between cells.…”