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Cathepsin X cleaves the beta2 cytoplasmic tail of LFA-1 inducing the intermediate affinity form of LFA-1 and alpha-actinin-1 binding.

Authors
  • Jevnikar, Zala
  • Obermajer, Natasa
  • Pecar-Fonović, Ursa
  • Karaoglanovic-Carmona, Adriana
  • Kos, Janko
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Nov 01, 2009
Volume
39
Issue
11
Pages
3217–3227
Identifiers
DOI: 10.1002/eji.200939562
PMID: 19750481
Source
Medline
License
Unknown

Abstract

The motility of T cells depends on the dynamic spatial regulation of integrin-mediated adhesion and de-adhesion. Cathepsin X, a cysteine protease, has been shown to regulate T-cell migration by interaction with lymphocyte function associated antigen-1 (LFA-1). LFA-1 adhesion to the ICAM-1 is controlled by the association of actin-binding proteins with the cytoplasmic tail of the beta(2) chain of LFA-1. Cleavage by cathepsin X of the amino acid residues S(769), E(768) and A(767) from the C-terminal of the beta(2) cytoplasmic tail of LFA-1 is shown to promote binding of the actin-binding protein alpha-actinin-1. Furthermore, cathepsin X overexpression reduced LFA-1 clustering and induced an intermediate affinity LFA-1 conformation that is known to associate with alpha-actinin-1. Increased levels of intermediate affinity LFA-1 resulted in augmented cell spreading due to reduced attachment of T cells to the ICAM-1-coated surface. Gradual cleavage of LFA-1 by cathepsin X enables the transition between intermediate and high affinity LFA-1, an event that is crucial for effective T-cell migration.

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