Format

Send to

Choose Destination
J Cell Sci. 2014 Sep 15;127(Pt 18):3983-97. doi: 10.1242/jcs.149336. Epub 2014 Jul 18.

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

Author information

1
EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France cornelia.wilson@unilim.fr.
2
EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France.
3
EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87000 Limoges CEDEX-France.
4
Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87000 Limoges CEDEX-France.

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.

KEYWORDS:

Angiogenesis; Cancer; EGFR; Exosome; NTRK2; Sortilin; TrkB

PMID:
25037567
DOI:
10.1242/jcs.149336
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center