title: LFA-1 fine-tuning by cathepsin X.
abstract: The adhesion molecule lymphocyte function-associated antigen (LFA)-1 plays a key role in immune surveillance and response. Its conformation is spatially and temporally regulated, enabling adhesion and deadhesion during T-cell migration. LFA-1 adhesion to its major ligand intercellular adhesion molecule 1 is controlled by adaptor proteins which bind the cytoplasmic tail of the β (2) subunit. Cathepsin X, a cysteine carboxypeptidase, promotes T-cell migration and morphological changes by cleaving the β (2) cytoplasmic tail of LFA-1. In this way, it modulates the affinity of LFA-1 for structural adaptors talin-1 and α-actinin-1 and enables the stepwise transition between intermediate and high-affinity conformations of LFA-1, an event that is necessary for effective T-cell function. Cathepsin X regulation that would allow precise modulation of LFA-1 affinity has a great potential for anti-LFA-1 therapy.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. zala.jevnikar@ffa.uni-lj.si
authors.forename: Zala
authors.initials: Z
authors.lastname: Jevnikar
authors.forename: Nataša
authors.initials: N
authors.lastname: Obermajer
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000185:Actinin / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000276:immunology*; D007157:Immunologic Surveillance / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*; D016608:Talin / Q000378:metabolism
chemical_list: C526905:ACTN1 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; C518832:TLN1 protein, human; D016608:Talin; D000185:Actinin; D002403:Cathepsins