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 beta1 and beta3 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 beta1 integrins, including the fibronectin receptor alpha5beta1. To investigate this, we characterized the beta1 integrin synthesized in cells expressing talin anti-sense RNA (AT22 cells). We identified a large intracellular pool of beta1 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 alpha5beta1. In normal cells, talin was found associated with beta1 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 alpha chains.
Martel
V
V
Laboratoire d'Etude de la Différenciation et de l'Adhérence Cellulaires, UMR CNRS/UJF 5538, Institut Albert Bonniot, Faculté de médecine, Domaine de la Merci, France.
Vignoud
L
L
Dupé
S
S
Frachet
P
P
Block
M R
MR
Albigès-Rizo
C
C
D016375:Antisense Elements (Genetics); D001692:Biological Transport / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D008861:Microsomes / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D016608:Talin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016375:Antisense Elements (Genetics); D017469:Receptors, Fibronectin; D016608:Talin