Talin controls the exit of the integrin alpha(5)beta(1) from an early compartment of the secretory pathway

Talin is a major cytosolic protein that links the intracellular domains of beta(1) and beta(3) integrins to the cytoskeleton. It is required for focal adhesion assembly, However, its downregulation not only slows down cell sp reading and organization of focal adhesions but also impairs the maturation of some beta(1) integrins, including the fibronectin receptor alpha(5)beta (1) To investigate this, we characterized the beta(1) integrin synthesized in cells expressing talin anti-sense RNA (AT22 cells), We identified a larg e intracellular pool of beta(1) integrins that is abnormally accumulated in an earlier compartment of the secretory pathway. In this report, we show t hat in talin-deficient AT22 cells, the aberrant glycosylation of integrin r eceptors is accompanied by a delay in the export of the integrin alpha(5)be ta(1), In normal cells, talin was found associated with beta(1) integrins i n an enriched membrane fraction containing Golgi and endoplasmic reticulum, Finally, microinjection of anti-talin antibodies resulted in accumulation of the integrins within the cells, These data strongly suggest that talin p lays a specific role in the export of newly synthesized integrins, We propo se that talin binding to the integrin may disclose a diphenylalanine export signal, which is present in the membrane-proximal GFFKR motif conserved in all integrin alpha chains.