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Structural Basis of β2 Integrin Inside—Out Activation

β2 integrins are expressed on all leukocytes. Precise regulation of the β2 integrin is critical for leukocyte adhesion and trafficking. In neutrophils, β2 integrins participate in slow rolling. When activated by inside–out signaling, fully activated β2 integrins mediate rapid leukocyte arrest and ad...

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Detalles Bibliográficos
Autores principales: Wen, Lai, Lyu, Qingkang, Ley, Klaus, Goult, Benjamin T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564206/
https://www.ncbi.nlm.nih.gov/pubmed/36231001
http://dx.doi.org/10.3390/cells11193039
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author Wen, Lai
Lyu, Qingkang
Ley, Klaus
Goult, Benjamin T.
author_facet Wen, Lai
Lyu, Qingkang
Ley, Klaus
Goult, Benjamin T.
author_sort Wen, Lai
collection PubMed
description β2 integrins are expressed on all leukocytes. Precise regulation of the β2 integrin is critical for leukocyte adhesion and trafficking. In neutrophils, β2 integrins participate in slow rolling. When activated by inside–out signaling, fully activated β2 integrins mediate rapid leukocyte arrest and adhesion. The two activation pathways, starting with selectin ligand engagement and chemokine receptor ligation, respectively, converge on phosphoinositide 3-kinase, talin-1, kindlin-3 and Rap1. Here, we focus on recent structural insights into autoinhibited talin-1 and autoinhibited trimeric kindlin-3. When activated, both talin-1 and kindlin-3 can bind the β2 cytoplasmic tail at separate but adjacent sites. We discuss possible pathways for talin-1 and kindlin-3 activation, recruitment to the plasma membrane, and their role in integrin activation. We propose new models of the final steps of integrin activation involving the complex of talin-1, kindlin-3, integrin and the plasma membrane.
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spelling pubmed-95642062022-10-15 Structural Basis of β2 Integrin Inside—Out Activation Wen, Lai Lyu, Qingkang Ley, Klaus Goult, Benjamin T. Cells Review β2 integrins are expressed on all leukocytes. Precise regulation of the β2 integrin is critical for leukocyte adhesion and trafficking. In neutrophils, β2 integrins participate in slow rolling. When activated by inside–out signaling, fully activated β2 integrins mediate rapid leukocyte arrest and adhesion. The two activation pathways, starting with selectin ligand engagement and chemokine receptor ligation, respectively, converge on phosphoinositide 3-kinase, talin-1, kindlin-3 and Rap1. Here, we focus on recent structural insights into autoinhibited talin-1 and autoinhibited trimeric kindlin-3. When activated, both talin-1 and kindlin-3 can bind the β2 cytoplasmic tail at separate but adjacent sites. We discuss possible pathways for talin-1 and kindlin-3 activation, recruitment to the plasma membrane, and their role in integrin activation. We propose new models of the final steps of integrin activation involving the complex of talin-1, kindlin-3, integrin and the plasma membrane. MDPI 2022-09-28 /pmc/articles/PMC9564206/ /pubmed/36231001 http://dx.doi.org/10.3390/cells11193039 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wen, Lai
Lyu, Qingkang
Ley, Klaus
Goult, Benjamin T.
Structural Basis of β2 Integrin Inside—Out Activation
title Structural Basis of β2 Integrin Inside—Out Activation
title_full Structural Basis of β2 Integrin Inside—Out Activation
title_fullStr Structural Basis of β2 Integrin Inside—Out Activation
title_full_unstemmed Structural Basis of β2 Integrin Inside—Out Activation
title_short Structural Basis of β2 Integrin Inside—Out Activation
title_sort structural basis of β2 integrin inside—out activation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564206/
https://www.ncbi.nlm.nih.gov/pubmed/36231001
http://dx.doi.org/10.3390/cells11193039
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