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Structural Basis of β2 Integrin Inside—Out Activation

Wen, Lai, Qingkang, Lyu, Ley, Klaus, Goult, Benjamin T (2022) Structural Basis of β2 Integrin Inside—Out Activation. Cells, 11 (19). Article Number 3039. ISSN 2073-4409. (doi:10.3390/cells11193039) (KAR id:97172)

Abstract

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.

Item Type: Article
DOI/Identification number: 10.3390/cells11193039
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords: integrin; talin; kindlin; activation; Rap1; leukocytes; neutrophils; chemokine; structural biology; cell adhesion
Subjects: Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Cancer Research UK (https://ror.org/054225q67)
National Institutes of Health (https://ror.org/01cwqze88)
Depositing User: Ben Goult
Date Deposited: 28 Sep 2022 17:37 UTC
Last Modified: 12 Dec 2023 14:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/97172 (The current URI for this page, for reference purposes)

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