Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors.

Abstract

The transfer of exosomes containing both genetic and protein materials is necessary for the control of the cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, and the mechanism of their action in membrane transport and related signaling events are not clearly understood. In this study, we demonstrate, in human lung cancer A549 cells, that the exosome release mechanism is closely linked to the multifaceted receptor sortilin (also called neurotensin receptor 3). Sortilin is already known to be important for cancer cell function. Here, we report for the first time its role in the assembly of a tyrosine kinase complex and subsequent exosome release. This new complex (termed the TES complex) is found in exosomes and results in the linkage of the two tyrosine kinase receptors TrkB (also known as NTRK2) and EGFR with sortilin. Using in vitro models, we demonstrate that this sortilin-containing complex exhibits a control on endothelial cells and angiogenesis activation through exosome transfer.

• Authors: Cornelia M Wilson, Thomas Naves, François Vincent, Boris Melloni, François Bonnaud, Fabrice Lalloué, Marie-Odile Jauberteau
• Journal: Journal of cell science (J Cell Sci) Vol. 127 Issue Pt 18 Pg. 3983-97 (Sep 15 2014) ISSN: 1477-9137 [Electronic] England
• PMID: 25037567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014. Published by The Company of Biologists Ltd.

Chemical References

• Adaptor Proteins, Vesicular Transport
• Membrane Glycoproteins
• EGFR protein, human
• ErbB Receptors
• Protein-Tyrosine Kinases
• Receptor, trkB
• tropomyosin-related kinase-B, human
• sortilin

Topics

• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Endothelial Cells (enzymology, metabolism)
• ErbB Receptors (genetics, metabolism)
• Exosomes (enzymology, metabolism)
• Humans
• Membrane Glycoproteins (genetics, metabolism)
• Protein Binding
• Protein-Tyrosine Kinases (genetics, metabolism)
• Receptor, trkB
• Signal Transduction