Nanotubes, exosomes, and nucleic acid-binding peptides provide novel mechanisms of intercellular communication in eukaryotic cells: implications in health and disease

Abstract

The prevailing view that eukaryotic cells are restrained from intercellular exchange of genetic information has been challenged by recent reports on nanotubes, exosomes, apoptotic bodies, and nucleic acid-binding peptides that provide novel pathways for cell-cell communication, with implications in health and disease.

Figure 1.

TNT-connecting cells. Jurkat T cells differentially labeled with the membrane dyes DiO (green) and DiL (red) were cocultured. The connecting TNT contains a junction, as shown by the distinct separation of the membrane dyes. Other nanotubes have, however, been shown to mediate membrane continuity between cells. Reprinted by permission from Macmillan Publishers Ltd., Nature Cell Biology (copyright 2008; Sowinski et al., 2008), and D.M. Davis (Imperial College, London, England, UK). Bar, 10 μm.

Figure 2.

Possible routes for nucleic acid exchange between cells. The classical mechanism of cellular communication via macromolecules is through secretion of signaling molecules. Secreted molecules are usually relayed through a secretory vesicular compartment (1) that subsequently fuses with the plasma membrane. Exosomes are released in a similar fashion, whereas microvesicles bud off directly from the plasma membrane. Such vesicles have been shown to contain nucleic acids (2) that hereby can be shuttled between cells. The mechanism of vesicular cargo uptake by recipient cells is largely unknown but may involve either direct membrane fusion or endocytosis (3). The internalization mechanisms of free peptide or protein bound nucleic acids have been better studied and may involve proteoglycan-dependent endocytosis (4). How endocytosed macromolecules escape the endosome and gain access to the cytoplasm remains ill-defined, but recent findings suggest a role for SID-1 in nucleic acid membrane transfer (5). Internalized vesicles might also intersect with the exosomal biogenesis machinery in late endosomes/multivesicular bodies (6), thus giving rise to compound vesicles that can deliver an integrated message to yet other cells (shown in blue). An alternative pathway for macromolecular shuttling between cells is through TNTs (7). Vesicles of endosomal origin are among the cargos demonstrated to be transported via this pathway. However, a multitude of other cargos, including nucleic acids and proteins, are potentially sorted for intercellular transport via TNTs. Finally, it has been demonstrated that apoptotic bodies released from tumor cells (8) can deliver oncogenic DNA and transform nonmalignant, surrounding cells.