Trans-endocytosis from filopodia: How ephrins surf between cells to be remembered

Date

Feb 8, 2019

Time

11:00 AM - 12:00 PM

Speaker

José Ignacio Valenzuela Iturra

Affiliation

Institut Curie, CNRS - UMR144, Paris, France

Language

en

Main Topic

Biologie

Other Topics

Biologie

Host

Marino Zerial

Description

Ephrins can elicit either contact-mediated cell-cell adhesion or repulsion depending on the efficiency of removal of their ligand/receptor complexes from the cell surface, thus controlling tissue morphogenesis and oncogenic development. However, the dynamic of turnover of the newly assembled ephrin/Eph-receptor complexes during cell-cell interactions remains mostly unexplored. By using the RUSH (Retention Using Selective Hooks) system, we show that ephrin-A1/EphA2 complexes are locally formed at the tip of cytoneme-like filopodia, at cell-to-cell contacts. Clusters of ephrin-A1 from donor cells surf on filopodia associated to EphA2-bearing sub-domains of acceptor cells. Full-length ephrin-A1 is transferred to acceptor cells by trans-endocytosis through a proteolysis-independent mechanism. Trans-endocytosed ephrin-A1 bound to its receptor enables signaling to be emitted from endo-lysosomes of acceptor cells even after cell division. Localized trans-endocytosis of ephrin-A1 sustains contact-mediated repulsion on cancer cells. Our results uncover the essential role played by local concentration at the tip of filopodia and the trans-endocytosis of full-length ephrin to maintain a memory of ephrin signaling.

Last modified: Feb 9, 2019, 1:07:40 AM