Structural Basis of β2 Integrin Inside-Out Activation.

Wen, Lai, Lyu, Qingkang, Ley, Klaus and Goult, Benjamin T ORCID: 0000-0002-3438-2807 (2022) Structural Basis of β2 Integrin Inside-Out Activation. Cells, 11 (19). p. 3039.

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Official URL: http://dx.doi.org/10.3390/cells11193039

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
Uncontrolled Keywords:	Talin, Selectins, Receptors, Chemokine, Integrins, Ligands, Phosphatidylinositol 3-Kinases, Phosphatidylinositol 3-Kinase, CD18 Antigens
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	06 Mar 2024 11:17
Last Modified:	06 Mar 2024 11:17
DOI:	10.3390/cells11193039
Open Access URL:	https://doi.org/10.3390/cells11193039
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179193