Talin controls the exit of the integrin α₅β₁ from an early compartment of the secretory pathway Available to Purchase

Talin is a major cytosolic protein that links the intracellular domains of β₁ and β₃ integrins to the cytoskeleton. It is required for focal adhesion assembly. However, its downregulation not only slows down cell spreading and organization of focal adhesions but also impairs the maturation of some β₁ integrins, including the fibronectin receptor α₅β₁. To investigate this, we characterized the β₁ integrin synthesized in cells expressing talin anti-sense RNA (AT22 cells). We identified a large intracellular pool of β₁ integrins that is abnormally accumulated in an earlier compartment of the secretory pathway. In this report, we show that in talin-deficient AT22 cells, the aberrant glycosylation of integrin receptors is accompanied by a delay in the export of the integrin α₅β₁. In normal cells, talin was found associated with β₁ integrins in 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 plays a specific role in the export of newly synthesized integrins. We propose 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 α chains.