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Vol. 13, Issue 11, 3845-3858, November 2002
6
4 Integrin in Keratinocytes
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX
Amsterdam, The Netherlands
The integrin 
6
4 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 64 in live cells two different 4-chimeras were
stably expressed in 4-deficient PA-JEB keratinocytes. One chimera
consisted of full-length 4 fused to EGFP at its carboxy terminus
(4-EGFP). In a second chimera the extracellular part of 4 was
replaced by EGFP (EGFP-4), 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 4-EGFP and EGFP-4 hemidesmosomes disappear, and a
proportion of the 4-EGFP, but not of the EGFP-4 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 4-EGFP migrate considerably more slowly than
those that express EGFP-4. Studies with a 4-EGFP mutant that is
unable to interact with plectin and thus with the cytoskeleton
(4R1281W-EGFP) suggest that the stabilization of the
interaction between 64 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 4 with plectin renders the bond between
64 and laminin-5 more stable, i.e., 4-EGFP is less dynamic
than 4R1281W-EGFP. On the other hand, when 64 is
bound to laminin-5, the binding dynamics of 4 to plectin are
increased, i.e., 4-EGFP is more dynamic than EGFP-4. We suggest
that the stability of the interaction between 64 and laminin-5 is
influenced by the clustering of 64 through the deposition of
laminin-5 underneath the cells. This clustering ultimately determines
whether 64 will inhibit cell migration or not.
Online
version of this article contains video material. Online version is
available at www.molbiolcell.org.
*
Corresponding author. E-mail address: a.sonnenberg{at}nki.nl.
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