Talin autoinhibition is required for morphogenesis. Stephanie J. Ellis¹, Jenny Long², Michael J. Fairchild¹, Paolo Lobo³, Stefan Czerniecki¹, Filip van Petegem³, Frieder Schöck², Guy Tanentzapf¹. 1) Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada; 2) Biology Department, McGill University, Montreal, PQ, Canada; 3) Department of Biochemistry, University of British Columbia, Vancouver, BC, Canada.

   FERM (4.1/Ezrin/Radixin/Moesin) domain proteins modulate cell shape and adhesion during morphogenesis by linking the plasma membrane and the actin cytoskeleton. Talin, a FERM-domain containing protein, forms a direct link between integrin adhesion receptors and the actin cytoskeleton. Similar to other FERM proteins, talin makes an intramolecular interaction that could autoinhibit the activity of talin. However, the functional consequence of such an interaction has not been previously explored in vivo. Here, we demonstrate that targeted disruption of talin autoinhibition impinges on morphogenetic movements during fly development. Autoinhibition-impaired talin is more stable at sites of integrin-ECM attachment, suggesting that talin autoinhibition is required to facilitate adhesion turnover during morphogenetic processes. Integrin is also stabilized at sites of adhesion when autoinhibition is blocked. Finally, we present evidence that talin autoinhibition is regulated by Rap1-dependent signaling. Based on our data we propose that talin autoinhibition provides a switch for modulating adhesion turnover and adhesion stability during morphogenesis.