Syndecan-1 interaction with the LG4/5 domain in laminin-332 is essential for keratinocyte migration

Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-I, we reveal that both syndecan-I and the alpha3beta I integrin bind to precursor LN332. We further demonstrate that syndecan-I mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-I expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta I integrin. We finally show that cell migration on pre-LN332 requires syndecan- I. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility. J. Cell. Physiol. 214: 238-249, 2008. (c) 2007 Wiley-Liss, Inc.