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A more recent version of this article appeared on November 1, 2002
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Submitted on January 3, 2002
Revised on August 8, 2002
Accepted on August 14, 2002
6ß4 integrin in keratinocytes
1 Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
* Corresponding author. E-mail address: a.sonnenberg{at}nki.nl.
The integrin 
6ß4 has been implicated in two apparently contrasting processes, i.e. the formation of stable adhesions, and cell migration and invasion. To study the dynamic properties of 6ß4 in live cells two different ß4-chimeras were stably expressed in ß4-deficient PA-JEB keratinocytes. One chimera consisted of full-length ß4 fused to EGFP at its carboxy terminus (ß4-EGFP). In a second chimera the extracellular part of ß4 was replaced by EGFP (EGFP-ß4), thereby rendering it incapable of associating with 6 and thus of binding to laminin-5. Both chimeras induce the formation of hemidesmosome-like structures, which contain plectin and often also BP180 and BP230. During cell migration and -division, the ß4-EGFP and EGFP-ß4 hemidesmosomes disappear, and a proportion of the ß4-EGFP, but not of the EGFP-ß4 molecules, become part of retraction fibers, which are occasionally ripped from the cell membrane, thereby leaving "footprints" of the migrating cell. PA-JEB cells expressing ß4-EGFP migrate considerably more slowly than those that express EGFP-ß4. Studies with a ß4-EGFP mutant that is unable to interact with plectin and thus with the cytoskeleton (ß4R1281W-EGFP) suggest that the stabilization of the interaction between 6ß4 and LN-5, rather than the increased adhesion to LN-5 is responsible for the inhibition of migration. Consistent with this, photobleaching and recovery experiments revealed that the interaction of ß4 with plectin renders the bond between 6ß4 and laminin-5 more stable, i.e. ß4-EGFP is less dynamic than ß4R1281W-EGFP. On the other hand, when 6ß4 is bound to laminin-5, the binding dynamics of ß4 to plectin are increased, i.e. ß4-EGFP is more dynamic than EGFP-ß4. We suggest that the stability of the interaction between 6ß4 and laminin-5 is influenced by the clustering of 6ß4 through the deposition of laminin-5 underneath the cells. This clustering ultimately determines whether 6ß4 will inhibit cell migration or not.
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