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

Belting M, Wittrup A - J. Cell Biol. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Lund University, Department of Clinical Sciences, Section of Oncology, Barngatan 2:1, SE-221 85 Lund, Sweden.

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC2606965&req=5

fig2: 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.

Mentions: Our molecular understanding of endocytotic and intracellular sorting mechanisms, the dynamics of multivesicular bodies and exocytosis, and the composition of biological membranes have increased considerably over the past few years. As for the pathophysiological function of membrane transport pathways in mammalian cells, most studies have focused on the internalization and trafficking of foreign intruders, i.e., bacteria and viruses, and more lately on nonnatural, synthetic peptides and lipids for therapeutic nucleic acid delivery. The studies discussed here provide a framework for the existence of intrinsic membrane transport pathways for the intercellular exchange of nucleic acids locally and at the systemic level in multicellular organisms (Fig. 2). This raises the central question of whether the observed phenomena are traces of evolutionary remnants or if they indeed reflect significant biological functions in modern mammalian organisms. What could these functions be? Although it is easy to appreciate the potential versatility of a nucleic acid–based communication system in higher organisms, we can only speculate at this point on the specific signals that are transmitted and their physiological roles.


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

Belting M, Wittrup A - J. Cell Biol. (2008)

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.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2606965&req=5

fig2: 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.
Mentions: Our molecular understanding of endocytotic and intracellular sorting mechanisms, the dynamics of multivesicular bodies and exocytosis, and the composition of biological membranes have increased considerably over the past few years. As for the pathophysiological function of membrane transport pathways in mammalian cells, most studies have focused on the internalization and trafficking of foreign intruders, i.e., bacteria and viruses, and more lately on nonnatural, synthetic peptides and lipids for therapeutic nucleic acid delivery. The studies discussed here provide a framework for the existence of intrinsic membrane transport pathways for the intercellular exchange of nucleic acids locally and at the systemic level in multicellular organisms (Fig. 2). This raises the central question of whether the observed phenomena are traces of evolutionary remnants or if they indeed reflect significant biological functions in modern mammalian organisms. What could these functions be? Although it is easy to appreciate the potential versatility of a nucleic acid–based communication system in higher organisms, we can only speculate at this point on the specific signals that are transmitted and their physiological roles.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Lund University, Department of Clinical Sciences, Section of Oncology, Barngatan 2:1, SE-221 85 Lund, Sweden.

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.

Show MeSH
Related in: MedlinePlus