Distinct developmental roles for direct and indirect talin-mediated linkage to actin.
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.
Franco-Cea
Ari
A
Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Ellis
Stephanie J
SJ
Fairchild
Michael J
MJ
Yuan
Lin
L
Cheung
Tsz Ying Sylvia
TY
Tanentzapf
Guy
G
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
D000199:Actins; D029721:Drosophila Proteins; D016023:Integrins; D016608:Talin; D049452:Green Fluorescent Proteins