Cysteine protease-mediated cytoskeleton interactions with LFA-1 promote T-cell morphological changes.
Cell Motil Cytoskeleton
; 66(11): 1030-40, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19670215
ABSTRACT
T cells migrate through restrictive barriers in a protease-independent, amoeboid fashion that is characterized by morphological cell polarization. The interaction of cysteine-dependent carboxypeptidase cathepsin X with beta(2) integrin LFA-1 (lymphocyte function associated antigen 1) induces T-cell morphological changes, displaying into a 3D extracellular matrix a cytoplasmic projection termed a uropod. In the present study we show that inhibition of cathepsin X and a cysteine-dependent endopeptidase, cathepsin L, markedly inhibits T-cell actin polymerization, shape polarization, and chemotaxis. We propose that cathepsin L promotes T-cell migration associated processes by activating procathepsin X in the endolysosomal vesicles near the cell membrane and at the peak of the uropod, where both proteases were colocalized. We show that active cathepsin X modifies the beta(2) cytoplasmic tail of LFA-1 in the uropod, promoting its high affinity conformation. We suggest that LFA-1 cleavage contributes to the conformational change in the cytoplasmic tail, promoting the binding of the cytoskeletal protein talin. This interaction is restricted to the uropod and results in the stabilization of this region, promoting LFA-1-mediated cell uropod elongation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Catepsinas
/
Antígeno-1 Associado à Função Linfocitária
/
Actinas
/
Cisteína Proteases
Limite:
Humans
Idioma:
En
Revista:
Cell Motil Cytoskeleton
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Eslovênia