title: In vivo quantitative analysis of Talin turnover in response to force.
abstract: Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell-ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell-ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development.
authors.affiliation: Department of Cellular and Physiological Sciences, Life Science Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Guðlaug Katrín
authors.initials: GK
authors.lastname: Hákonardóttir
authors.affiliation: Department of Cellular and Physiological Sciences, Life Science Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Pablo
authors.initials: P
authors.lastname: López-Ceballos
authors.affiliation: Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada.
authors.forename: Alejandra Donají
authors.initials: AD
authors.lastname: Herrera-Reyes
authors.affiliation: Department of Integrative Biology, University of Colorado Denver, Denver, CO 80204.
authors.forename: Raibatak
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Coombs
authors.affiliation: Department of Cellular and Physiological Sciences, Life Science Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada tanentz@mail.ubc.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Tanentzapf
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D021982:Cell-Matrix Junctions / Q000378:metabolism; D004330:Drosophila; D005109:Extracellular Matrix / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D013312:Stress, Physiological / Q000502:physiology*; D016608:Talin / Q000378:metabolism*
chemical_list: D016023:Integrins; D016608:Talin