title: Talin autoinhibition is required for morphogenesis.
abstract: The establishment of a multicellular body plan requires coordinating changes in cell adhesion and the cytoskeleton to ensure proper cell shape and position within a tissue. Cell adhesion to the extracellular matrix (ECM) via integrins plays diverse, essential roles during animal embryogenesis and therefore must be precisely regulated. Talin, a FERM-domain containing protein, forms a direct link between integrin adhesion receptors and the actin cytoskeleton and is an important regulator of integrin function. Similar to other FERM proteins, talin makes an intramolecular interaction that could autoinhibit its activity. However, the functional consequence of such an interaction has not been previously explored in vivo. Here, we demonstrate that targeted disruption of talin autoinhibition gives rise to morphogenetic defects during fly development and specifically that dorsal closure (DC), a process that resembles wound healing, is delayed. Impairment of autoinhibition leads to reduced talin turnover at and increased talin and integrin recruitment to sites of integrin-ECM attachment. 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 that is essential for morphogenesis.
authors.affiliation: Department of Cellular and Physiological Sciences, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Ellis
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fairchild
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Harris
authors.forename: Jenny
authors.initials: J
authors.lastname: Long
authors.forename: Paolo
authors.initials: P
authors.lastname: Lobo
authors.forename: Stefan
authors.initials: S
authors.lastname: Czerniecki
authors.forename: Filip
authors.initials: F
authors.lastname: Van Petegem
authors.forename: Frieder
authors.initials: F
authors.lastname: Schöck
authors.forename: Mark
authors.initials: M
authors.lastname: Peifer
authors.forename: Guy
authors.initials: G
authors.lastname: Tanentzapf
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation; D015398:Signal Transduction; D016608:Talin / Q000235:genetics* / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D016608:Talin; D020827:rap1 GTP-Binding Proteins