L. Vignoud et al., NPXY MOTIFS CONTROL THE RECRUITMENT OF THE ALPHA-5-BETA-1 INTEGRIN INFOCAL ADHESIONS INDEPENDENTLY OF THE ASSOCIATION OF TALIN WITH THE BETA-1 CHAIN, Journal of Cell Science, 110, 1997, pp. 1421-1430
With the exception of the divergent beta 4 and beta 8 chains, the inte
grin beta subunit cytoplasmic domains are short and highly conserved s
equences, Consensus motifs are found among the different cytoplasmic b
eta chains. Experiments using chimeric receptors demonstrated that the
47 amino acids of the beta 1 subunit cytoplasmic domain contain suffi
cient information to target integrins to adhesion plaques, Three clust
ers of amino acids, named cyto-l, cyto-2 and cyto-3, seem to contribut
e to this localization, Cyto-2 and cyto-3 exhibit NPXY motifs, At pres
ent, the exact function of these motifs remains unknown but it is like
ly that these sequences are involved in protein-protein interactions,
Although NPXY motifs often act as internalization signals at the cytop
lasmic tall of membrane receptors, our previous results showed that th
e two NPXY motifs are not responsible for the alpha 5 beta 1 integrin
endocytosis. Herein, we address the question of the role of the two hi
ghly conserved NPXY motifs found in the beta 1 cytoplasmic domain, and
which correspond to the conserved domains cyto-2 and cyto-3, We demon
strate that, within the integrin beta 1 cytoplasmic tail, the two NPXY
motifs are required for the recruitment of the integrin in focal adhe
sions, In addition, our results indicate that these two motifs control
but do not belong to the talin-binding sites, Finally, the analysis o
f the phenotypes of NPXY mutants reveals that the interaction of talin
with the beta 1 cytosolic domain is not sufficient to target the inte
grins to focal adhesions.