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J Biol Chem, Vol. 275, Issue 8, 5249-5252, February 25, 2000

ACCELERATED PUBLICATION
Syndecan-4 Deficiency Impairs Focal Adhesion Formation Only under Restricted Conditions^*

Kazuhiro Ishiguro^§, Kenji Kadomatsu, Tetsuhito Kojima^§¶, Hisako Muramatsu, Shinobu Tsuzuki^§, Eishin Nakamura^§, Kazuo Kusugami^§, Hidehiko Saito^§, and Takashi Muramatsu

From the  Department of Biochemistry and the ^§ First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan and the ^¶ Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya 461-8673, Japan

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.

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^* This work was supported by grants-in-aid for scientific research from the Ministry of Education, Science, Sports and Culture of Japan (10175102, 1017211, 10CE2006, and 10557090), the Ministry of Health and Welfare of Japan, and Sankyo Foundation of Life Science.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel: 81-52-744-2059; Fax: 81-52-744-2065; E-mail: tmurama@tsuru.med.nagoya-u.ac.jp.

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Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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