Cathepsin X cleaves the beta2 cytoplasmic tail of LFA-1 inducing the intermediate affinity form of LFA-1 and alpha-actinin-1 binding.
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.
Jevnikar
Zala
Z
Faculty of Pharmacy, University of Ljubljana, Askerceva, Ljubljana, Slovenia. zala.Jevnikar@ffa.uni-lj.si
Obermajer
Natasa
N
Pecar-Fonović
Ursa
U
Karaoglanovic-Carmona
Adriana
A
Kos
Janko
J
D000185:Actinin / Q000276:immunology / Q000378:metabolism*; D002403:Cathepsins / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
C526905:ACTN1 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D000185:Actinin; D018799:Intercellular Adhesion Molecule-1; D002403:Cathepsins