Integrin-dependent YAP signaling requires LAMTOR1 mediated delivery of Src to the plasma membrane

Abstract

YAP signaling has emerged as an important signaling pathway involved in several normal and pathological processes. While main upstream effectors regulating its activity have been extensively studied, the interplay with other cellular processes has been far less analyzed. Here, we identified the LAMTOR complex as a new important regulator of YAP signaling. We uncovered that p18/LAMTOR1 is required for the recycling of Src on late endosomes to the cell periphery, and consequently to activate a signaling cascade that eventually controls YAP nuclear shuttling. Moreover, p18/LAMTOR1 positives late endosomes distribution is controlled by {beta}1 integrins, extracellular matrix stiffness and cell contractility. This likely relies on the targeting of microtubules to {beta}1 positive focal adhesion via ILK. Altogether our findings identify the late endosomal recycling pathway as a major regulator of YAP.