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

Cornelia Wilson (1) , Thomas Naves (1) , François Vincent (2) , Boris Melloni (2) , François Bonnaud (2) , Fabrice Lalloué (1, 3) , Marie-Odile Jauberteau-Marchan (1, 4)

1 HCP - Homéostasie Cellulaire et Pathologies
2 Service de Pathologie respiratoire et allergologie [CHU Limoges]
3 Service de Médecine interne A et polyclinique médicale [CHU Limoges]
4 Service d'Immunologie et immunogénétique [CHU Limoges]

: The transfer of exosomes containing both genetic and protein materials is necessary for the control of cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, their mechanisms 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 a multifaceted receptor, neurotensin (NT) receptor-3 also called sortilin. 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 novel complex (TES complex) found in exosomes results in the linkage of two tyrosine kinase receptors, TrkB and EGFR with sortilin. Using in vitro models, we demonstrate that this complex containing sortilin exhibits a control on endothelial cells and angiogenesis activation through exosome transfer.

Mots clés: Sortilin; Exosome; Cancer; EGFR; TrkB; NTRK2; Angiogenesis

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire

Cornelia Wilson, Thomas Naves, François Vincent, Boris Melloni, François Bonnaud, et al.. Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors.. Journal of Cell Science, 2014, 127 (18), epub ahead of print. ⟨10.1242/jcs.149336⟩. ⟨hal-01059696⟩