Cytoskeletal interactions with the leukocyte integrin cytoplasmic tail: Activation-dependent regulation of associations with talin and α-actinin

Rangarajan Sampath, Patricia J. Gallagher, Fredrick M. Pavalko

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

Circulating leukocytes are nonadherent but bind tightly to endothelial cells following activation. The increased avidity of leukocyte integrins for endothelial ligands following activation is regulated, in part, by interaction of the β2 subunit cytoplasmic tail with the actin cytoskeleton. We propose a mechanism to explain how tethering of the actin cytoskeleton to leukocyte integrins is regulated. In resting leukocytes, β2 integrins are constitutively linked to the actin cytoskeleton via the protein talin. Activation of cells induces proteolysis of talin and dissociation from the β2 tail. This phase is transient, however, and is followed by reattachment of actin filaments to integrins that is mediated by the protein α-actinin. The association of α-actinin with integrins may stabilize the cytoskeleton and promote firm adhesion to and migration across the endothelium. Glutathione S-transferase-β2 tail fusion protein/mutagenesis experiments suggest that the affinity of α-actinin binding to the β2 tail is regulated by a change in the conformation of the tail that unmasks a cryptic α- actinin binding domain. Positive and inhibitory domains within the β2 tail regulate α-actinin binding: a single 11-amino acid region (residues 736- 746) is necessary and sufficient for α-actinin binding, and a regulatory domain between residues 748-762 inhibits constitutive association of the β2 tail with α-actinin.

Original languageEnglish (US)
Pages (from-to)33588-33594
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number50
DOIs
StatePublished - Dec 11 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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