title: Talin1 regulates integrin turnover to promote embryonic epithelial morphogenesis.
abstract: Talin is a cytoskeletal protein that binds to integrin β cytoplasmic tails and regulates integrin activation. Talin1 ablation in mice disrupts gastrulation and causes embryonic lethality. However, the role of talin in mammalian epithelial morphogenesis is poorly understood. Here we demonstrate that embryoid bodies (EBs) differentiated from talin1-null embryonic stem cells are defective in integrin adhesion complex assembly, epiblast elongation, and lineage differentiation. These defects are accompanied by a significant reduction in integrin β1 protein levels due to accelerated degradation through an MG-132-sensitive proteasomal pathway. Overexpression of integrin β1 or MG-132 treatment in mutant EBs largely rescues the phenotype. In addition, epiblast cells isolated from talin1-null EBs exhibit impaired cell spreading and focal adhesion formation. Transfection of the mutant cells with green fluorescent protein (GFP)-tagged wild-type but not mutant talin1 that is defective in integrin binding normalizes integrin β1 protein levels and restores focal adhesion formation. Significantly, cell adhesion and spreading are also improved by overexpression of integrin β1. All together, these results suggest that talin1 binding to integrin promotes epiblast adhesion and morphogenesis in part by preventing integrin β1 degradation.
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School-UMDNJ, New Brunswick, New Jersey 08903, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaowen
authors.initials: X
authors.lastname: He
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Tian
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Monkley
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
authors.forename: Siobhan A
authors.initials: SA
authors.lastname: Corbett
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Lowry
authors.forename: Alan M
authors.initials: AM
authors.lastname: Graham
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D058732:Embryoid Bodies; D053595:Embryonic Stem Cells; D004848:Epithelium / Q000196:embryology; D022001:Focal Adhesions; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D055550:Protein Stability; D016608:Talin / Q000502:physiology*
chemical_list: D019012:Integrin beta1; D016023:Integrins; D016608:Talin; C496077:Tln1 protein, mouse