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Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem

Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1)...

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Autores principales: Gingras, Alexandre R., Lagarrigue, Frederic, Cuevas, Monica N., Valadez, Andrew J., Zorovich, Marcus, McLaughlin, Wilma, Lopez-Ramirez, Miguel Alejandro, Seban, Nicolas, Ley, Klaus, Kiosses, William B., Ginsberg, Mark H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548133/
https://www.ncbi.nlm.nih.gov/pubmed/30988001
http://dx.doi.org/10.1083/jcb.201810061
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author Gingras, Alexandre R.
Lagarrigue, Frederic
Cuevas, Monica N.
Valadez, Andrew J.
Zorovich, Marcus
McLaughlin, Wilma
Lopez-Ramirez, Miguel Alejandro
Seban, Nicolas
Ley, Klaus
Kiosses, William B.
Ginsberg, Mark H.
author_facet Gingras, Alexandre R.
Lagarrigue, Frederic
Cuevas, Monica N.
Valadez, Andrew J.
Zorovich, Marcus
McLaughlin, Wilma
Lopez-Ramirez, Miguel Alejandro
Seban, Nicolas
Ley, Klaus
Kiosses, William B.
Ginsberg, Mark H.
author_sort Gingras, Alexandre R.
collection PubMed
description Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1) contains a previously undetected Rap1-binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that has a propensity to form a helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical, as charge-reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1-binding site and a transient lipid-dependent helix in F1 work in tandem to enable a direct Rap1–talin1 interaction to cause integrin activation.
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spelling pubmed-65481332019-12-28 Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem Gingras, Alexandre R. Lagarrigue, Frederic Cuevas, Monica N. Valadez, Andrew J. Zorovich, Marcus McLaughlin, Wilma Lopez-Ramirez, Miguel Alejandro Seban, Nicolas Ley, Klaus Kiosses, William B. Ginsberg, Mark H. J Cell Biol Research Articles Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1) contains a previously undetected Rap1-binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that has a propensity to form a helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical, as charge-reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1-binding site and a transient lipid-dependent helix in F1 work in tandem to enable a direct Rap1–talin1 interaction to cause integrin activation. Rockefeller University Press 2019-06-28 2019-04-15 /pmc/articles/PMC6548133/ /pubmed/30988001 http://dx.doi.org/10.1083/jcb.201810061 Text en © 2019 Gingras et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Gingras, Alexandre R.
Lagarrigue, Frederic
Cuevas, Monica N.
Valadez, Andrew J.
Zorovich, Marcus
McLaughlin, Wilma
Lopez-Ramirez, Miguel Alejandro
Seban, Nicolas
Ley, Klaus
Kiosses, William B.
Ginsberg, Mark H.
Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title_full Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title_fullStr Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title_full_unstemmed Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title_short Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
title_sort rap1 binding and a lipid-dependent helix in talin f1 domain promote integrin activation in tandem
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548133/
https://www.ncbi.nlm.nih.gov/pubmed/30988001
http://dx.doi.org/10.1083/jcb.201810061
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