Publications by authors named "Alejandra Donaji Herrera-Reyes"

2 Publications

  • Page 1 of 1

In vivo regulation of integrin turnover by outside-in activation.

J Cell Sci 2016 08 16;129(15):2912-24. Epub 2016 Jun 16.

Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3

The development of three-dimensional tissue architecture requires precise control over the attachment of cells to the extracellular matrix (ECM). Integrins, the main ECM-binding receptors in animals, are regulated in multiple ways to modulate cell-ECM adhesion. One example is the conformational activation of integrins by extracellular signals ('outside-in activation') or by intracellular signals ('inside-out activation'), whereas another is the modulation of integrin turnover. We demonstrate that outside-in activation regulates integrin turnover to stabilize tissue architecture in vivo Treating Drosophila embryos with Mg(2+) and Mn(2+), known to induce outside-in activation, resulted in decreased integrin turnover. Mathematical modeling combined with mutational analysis provides mechanistic insight into the stabilization of integrins at the membrane. We show that as tissues mature, outside-in activation is crucial for regulating the stabilization of integrin-mediated adhesions. This data identifies a new in vivo role for outside-in activation and sheds light on the key transition between tissue morphogenesis and maintenance.
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http://dx.doi.org/10.1242/jcs.190256DOI Listing
August 2016

In vivo quantitative analysis of Talin turnover in response to force.

Mol Biol Cell 2015 Nov 7;26(22):4149-62. Epub 2015 Oct 7.

Department of Cellular and Physiological Sciences, Life Science Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

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.
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http://dx.doi.org/10.1091/mbc.E15-05-0304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710244PMC
November 2015