RalB directly triggers invasion downstream Ras by mobilizing the Wave complex

• DOI: 10.7554/elife.40474
• Publication Date: 2018-10-15T12:00:58Z
• Authors: Giulia Zago; Irina Veith; Manish Kumar Singh; Laetitia Fuhrmann; Simon De Beco; Amanda Remorino; Saori Takaoka; Marjorie Palmeri; Frédérique Berger; Nathalie Brandon; Ahmed El Marjou; Anne Vincent-Salomon; Jacques Camonis; Mathieu Coppey; Maria Carla Parrini
• Keywords: Exocyst

The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cancers; particular, RalB is involved invasion metastasis. However, therapies targeting signalling are not available yet. By a novel optogenetic approach, we found that light-controlled activation of at plasma-membrane promotes the recruitment Wave Regulatory Complex (WRC) via its effector exocyst, with consequent induction protrusions invasion. We show active signals to RalGEFs (Guanine nucleotide Exchange Factors), RGL1 RGL2, foster invasiveness; contribution appears be more important than MAPK PI3K pathways. Moreover, on clinical side, uncovered potential role breast cancers by determining expression protein level increases manner consistent progression toward This work highlights Ras-RGL1/2-RalB-exocyst-WRC axis as appealing target for anticancer strategies.