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

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.