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Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins

Interaction of talin with the cytoplasmic tails of integrin β triggers integrin activation, leading to an increase of integrin affinity/avidity for extracellular ligands. In talin KO mice, loss of talin interaction with platelet integrin αIIbβ3 causes a severe hemostatic defect, and loss of talin in...

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Autores principales: Liao, Zhongji, Gingras, Alexandre R., Lagarrigue, Frederic, Ginsberg, Mark H., Shattil, Sanford J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131925/
https://www.ncbi.nlm.nih.gov/pubmed/33865854
http://dx.doi.org/10.1016/j.jbc.2021.100675
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author Liao, Zhongji
Gingras, Alexandre R.
Lagarrigue, Frederic
Ginsberg, Mark H.
Shattil, Sanford J.
author_facet Liao, Zhongji
Gingras, Alexandre R.
Lagarrigue, Frederic
Ginsberg, Mark H.
Shattil, Sanford J.
author_sort Liao, Zhongji
collection PubMed
description Interaction of talin with the cytoplasmic tails of integrin β triggers integrin activation, leading to an increase of integrin affinity/avidity for extracellular ligands. In talin KO mice, loss of talin interaction with platelet integrin αIIbβ3 causes a severe hemostatic defect, and loss of talin interaction with endothelial cell integrin αVβ3 affects angiogenesis. In normal cells, talin is autoinhibited and localized in the cytoplasm. Here, we used an optogenetic platform to assess whether recruitment of full-length talin to the plasma membrane was sufficient to induce integrin activation. A dimerization module (Arabidopsis cryptochrome 2 fused to the N terminus of talin; N-terminal of cryptochrome-interacting basic helix-loop-helix domain ended with a CAAX box protein [C: cysteine; A: aliphatic amino acid; X: any C-terminal amino acid]) responsive to 450 nm (blue) light was inserted into Chinese hamster ovary cells and endothelial cells also expressing αIIbβ3 or αVβ3, respectively. Thus, exposure of the cells to blue light caused a rapid and reversible recruitment of Arabidopsis cryptochrome 2–talin to the N-terminal of cryptochrome-interacting basic helix-loop-helix domain ended with a CAAX box protein [C: cysteine; A: aliphatic amino acid; X: any C-terminal amino acid]–decorated plasma membrane. This resulted in β3 integrin activation in both cell types, as well as increasing migration of the endothelial cells. However, membrane recruitment of talin was not sufficient for integrin activation, as membrane-associated Ras-related protein 1 (Rap1)–GTP was also required. Moreover, talin mutations that interfered with its direct binding to Rap1 abrogated β3 integrin activation. Altogether, these results define a role for the plasma membrane recruitment of talin in β3 integrin activation, and they suggest a nuanced sequence of events thereafter involving Rap1–GTP.
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spelling pubmed-81319252021-05-24 Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins Liao, Zhongji Gingras, Alexandre R. Lagarrigue, Frederic Ginsberg, Mark H. Shattil, Sanford J. J Biol Chem Research Article Interaction of talin with the cytoplasmic tails of integrin β triggers integrin activation, leading to an increase of integrin affinity/avidity for extracellular ligands. In talin KO mice, loss of talin interaction with platelet integrin αIIbβ3 causes a severe hemostatic defect, and loss of talin interaction with endothelial cell integrin αVβ3 affects angiogenesis. In normal cells, talin is autoinhibited and localized in the cytoplasm. Here, we used an optogenetic platform to assess whether recruitment of full-length talin to the plasma membrane was sufficient to induce integrin activation. A dimerization module (Arabidopsis cryptochrome 2 fused to the N terminus of talin; N-terminal of cryptochrome-interacting basic helix-loop-helix domain ended with a CAAX box protein [C: cysteine; A: aliphatic amino acid; X: any C-terminal amino acid]) responsive to 450 nm (blue) light was inserted into Chinese hamster ovary cells and endothelial cells also expressing αIIbβ3 or αVβ3, respectively. Thus, exposure of the cells to blue light caused a rapid and reversible recruitment of Arabidopsis cryptochrome 2–talin to the N-terminal of cryptochrome-interacting basic helix-loop-helix domain ended with a CAAX box protein [C: cysteine; A: aliphatic amino acid; X: any C-terminal amino acid]–decorated plasma membrane. This resulted in β3 integrin activation in both cell types, as well as increasing migration of the endothelial cells. However, membrane recruitment of talin was not sufficient for integrin activation, as membrane-associated Ras-related protein 1 (Rap1)–GTP was also required. Moreover, talin mutations that interfered with its direct binding to Rap1 abrogated β3 integrin activation. Altogether, these results define a role for the plasma membrane recruitment of talin in β3 integrin activation, and they suggest a nuanced sequence of events thereafter involving Rap1–GTP. American Society for Biochemistry and Molecular Biology 2021-04-16 /pmc/articles/PMC8131925/ /pubmed/33865854 http://dx.doi.org/10.1016/j.jbc.2021.100675 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Liao, Zhongji
Gingras, Alexandre R.
Lagarrigue, Frederic
Ginsberg, Mark H.
Shattil, Sanford J.
Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title_full Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title_fullStr Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title_full_unstemmed Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title_short Optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
title_sort optogenetics-based localization of talin to the plasma membrane promotes activation of β3 integrins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131925/
https://www.ncbi.nlm.nih.gov/pubmed/33865854
http://dx.doi.org/10.1016/j.jbc.2021.100675
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