Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions.
Two domains of fibronectin deliver two different but cooperative signals required for focal adhesion formation. The signal from the cell-binding domain is mediated by integrins, whereas the signal from the heparin-binding domain is recognized by heparan sulfate proteoglycans, of which syndecan-4 has been hypothesized to be involved in focal adhesion formation. We generated mice deficient in syndecan-4 to study its role directly. Even in fibroblasts from syndecan-4-deficient mice, focal adhesions were formed, and actin fibers terminated normally at focal adhesions when they were cultured on coverslips coated with fibronectin or with a mixture of its cell-binding and heparin-binding fragments. However, when the cells were cultured on the cell-binding fragment and the heparin-binding fragment was added to the medium, focal adhesion formation was impaired in the syndecan-4 null fibroblasts as compared with that in wild-type cells. Therefore, syndecan-4 is essential for promoting focal adhesion formation only when the signal of the heparin-binding domain of fibronectin is delivered as a soluble form, most probably from the apical surface. When the signal is delivered as a substratum-bound form, other molecule(s) also participate(s) in the signal reception.
Ishiguro
K
K
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kadomatsu
K
K
Kojima
T
T
Muramatsu
H
H
Tsuzuki
S
S
Nakamura
E
E
Kusugami
K
K
Saito
H
H
Muramatsu
T
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002478:Cells, Cultured; D005091:Exons; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D053671:Syndecan-4; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D005353:Fibronectins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508304:SDC4 protein, human; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016596:Vinculin; D006493:Heparin