title: Distinct developmental roles for direct and indirect talin-mediated linkage to actin.
abstract: Transmembrane adhesion receptors, such as integrins, mediate cell adhesion by interacting with intracellular proteins that connect to the cytoskeleton. Talin, one such linker protein, is essential to connect extracellular matrix-bound integrins to the cytoskeleton. Talin can connect to the cytoskeleton either directly, through its actin-binding motifs, or indirectly, by recruiting other actin-binding proteins. Talin's carboxy-terminal end contains a well-characterized actin-binding domain (ABD). We tested the role of the C-terminal ABD of talin in integrin function in Drosophila. We found that introduction of mutations that reduced actin binding in vitro into the isolated C-terminal Talin-ABD impaired actin binding in vivo. Moreover, when engineered into full-length talin, these mutations disrupted a subset of integrin-mediated adhesion-dependent developmental events. Specifically, morphogenetic processes that involve dynamic, short-term integrin-mediated adhesion were particularly sensitive to impaired function of the C-terminal Talin-ABD. We propose that during development talin connects integrins to the cytoskeleton in distinct ways in different types of integrin-mediated adhesion: directly in transient adhesions and indirectly in stable long-lasting adhesions. Our results provide insight into how a similar array of molecular components can contribute to diverse adhesive processes throughout development.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Ari
authors.initials: A
authors.lastname: Franco-Cea
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Ellis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fairchild
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Tsz Ying Sylvia
authors.initials: TY
authors.lastname: Cheung
authors.forename: Guy
authors.initials: G
authors.lastname: Tanentzapf
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D016608:Talin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D016023:Integrins; D016608:Talin; D049452:Green Fluorescent Proteins