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


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
03 06 2019
Historique:
received: 12 10 2018
revised: 11 02 2019
accepted: 28 03 2019
pubmed: 17 4 2019
medline: 10 4 2020
entrez: 17 4 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30988001
pii: jcb.201810061
doi: 10.1083/jcb.201810061
pmc: PMC6548133
doi:

Substances chimiques

Integrins 0
Lipids 0
Shelterin Complex 0
TERF2IP protein, human 0
TLN1 protein, human 0
Talin 0
Telomere-Binding Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1799-1809

Subventions

Organisme : NHLBI NIH HHS
ID : K01 HL133530
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL078784
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL139947
Pays : United States
Organisme : NIH HHS
ID : S10 OD021831
Pays : United States

Informations de copyright

© 2019 Gingras et al.

Références

Cell. 2002 Sep 20;110(6):673-87
pubmed: 12297042
Science. 2003 Oct 3;302(5642):103-6
pubmed: 14526080
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
Curr Biol. 2006 Sep 19;16(18):1796-806
pubmed: 16979556
J Immunol. 2006 Dec 1;177(11):7707-14
pubmed: 17114441
Cell. 2007 Jan 12;128(1):171-82
pubmed: 17218263
J Clin Invest. 2007 Aug;117(8):2250-9
pubmed: 17627302
J Exp Med. 2007 Dec 24;204(13):3103-11
pubmed: 18086863
J Exp Med. 2007 Dec 24;204(13):3113-8
pubmed: 18086864
J Cell Sci. 2008 May 1;121(Pt 9):1345-7
pubmed: 18434644
J Biol Chem. 2009 Feb 20;284(8):5119-27
pubmed: 19098287
EMBO J. 2009 Nov 18;28(22):3623-32
pubmed: 19798053
J Cell Biol. 2010 Jan 11;188(1):157-73
pubmed: 20048261
EMBO J. 2010 Mar 17;29(6):1069-80
pubmed: 20150896
Nat Rev Mol Cell Biol. 2010 Apr;11(4):288-300
pubmed: 20308986
Blood. 1991 Jul 15;78(2):369-76
pubmed: 2070074
Blood. 2011 Feb 3;117(5):1719-22
pubmed: 20971947
Cell Res. 2012 Nov;22(11):1533-45
pubmed: 22710802
Nat Rev Mol Cell Biol. 2013 Aug;14(8):503-17
pubmed: 23860236
J Biol Chem. 1985 Sep 15;260(20):11107-14
pubmed: 2411729
Mol Cell Proteomics. 2014 Dec;13(12):3435-45
pubmed: 25205226
Blood. 2015 Jan 8;125(2):219-22
pubmed: 25336629
Blood. 2015 Dec 17;126(25):2695-703
pubmed: 26324702
Blood. 2015 Dec 17;126(25):2704-12
pubmed: 26337492
BMC Cell Biol. 2016 Jan 07;17:1
pubmed: 26744136
Structure. 2016 Dec 6;24(12):2152-2162
pubmed: 27839947
J Immunol. 2017 May 1;198(9):3410-3415
pubmed: 28348273
Nat Commun. 2017 Nov 23;8(1):1744
pubmed: 29170462
J Cell Biol. 2018 Apr 2;217(4):1453-1465
pubmed: 29535192
Blood. 2018 Nov 1;132(18):1951-1962
pubmed: 30131434
Blood Adv. 2018 Sep 25;2(18):2358-2368
pubmed: 30242097
Blood. 2018 Dec 27;132(26):2754-2762
pubmed: 30442677
J Cell Sci. 2018 Dec 18;131(24):null
pubmed: 30446511
J Cell Biol. 1994 Mar;124(6):1047-59
pubmed: 7510712

Auteurs

Alexandre R Gingras (AR)

Department of Medicine, University of California, San Diego, La Jolla, CA agingras@ucsd.edu.

Frederic Lagarrigue (F)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Monica N Cuevas (MN)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Andrew J Valadez (AJ)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Marcus Zorovich (M)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Wilma McLaughlin (W)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Miguel Alejandro Lopez-Ramirez (MA)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Nicolas Seban (N)

Department of Medicine, University of California, San Diego, La Jolla, CA.

Klaus Ley (K)

Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA.
Department of Bioengineering, University of California, San Diego, La Jolla, CA.

William B Kiosses (WB)

Microscopy Core Facility, La Jolla Institute for Immunology, La Jolla, CA.

Mark H Ginsberg (MH)

Department of Medicine, University of California, San Diego, La Jolla, CA mhginsberg@ucsd.edu.

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Classifications MeSH