Structural Basis of β2 Integrin Inside—Out Activation

Lai Wen, Qingkang Lyu, Klaus Ley, Benjamin T. Goult

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Article number3039
JournalCells
Volume11
Issue number19
DOIs
StatePublished - Oct 2022

Keywords

  • Rap1
  • activation
  • cell adhesion
  • chemokine
  • integrin
  • kindlin
  • leukocytes
  • neutrophils
  • structural biology
  • talin

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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