Structural and cell adhesion properties of zebrafish syndecan-4 are shared with higher vertebrates

James R. Whiteford, Sunggeon Ko, Weon Tae Lee, John R. Couchman

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The syndecan proteoglycans are an ancient class of receptor, bearing heparan sulfate chains that interact with numerous potential ligands including growth factors, morphogens, and extracellular matrix molecules. The single syndecan of invertebrates appears not to have cell adhesion roles, but these have been described for mammalian paralogues, especially syndecan-4. This member is best understood in terms of interactions, signaling, and structure of its cytoplasmic domain. The zebrafish homologue of syndecan-4 has been genetically linked to cell adhesion and migration in zebrafish embryos, but no molecular and cellular studies have been reported. Here it is demonstrated that key functional attributes of syndecan-4 are common to both zebrafish and mammalian homologues. These include glycosaminoglycan substitution, a NXIP motif in the extracellular domain that promotes integrin-mediated cell adhesion, and a transmembrane GXXXG motif that promotes dimer formation. In addition, despite some amino acid substitutions in the cytoplasmic domain, its ability to form twisted clamp dimers is preserved, as revealed by nuclear magnetic resonance spectroscopy. This technique also showed that phosphatidylinositol 4,5-bisphosphate can interact with the zebrafish syndecan-4 cytoplasmic domain, and that the molecule in its entirety supports focal adhesion formation, and complements the murine null cells to restore a normal actin cytoskeleton identically to the rat homologue. Therefore, the cell adhesion properties of syndecan-4 are consistent across the vertebrate spectrum and reflect an early acquisition of specialization after syndecan gene duplication events at the invertebrate/early chordate boundary.

Original languageEnglish
Pages (from-to)29322-29330
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number43
DOIs
Publication statusPublished - 2008 Oct 24

Fingerprint

Syndecan-4
Cell adhesion
Zebrafish
Cell Adhesion
Syndecans
Vertebrates
Dimers
Nonvertebrate Chordata
Substitution reactions
Bearings (structural)
Cytoplasmic Structures
Null Lymphocytes
Molecules
Focal Adhesions
Gene Duplication
Heparitin Sulfate
Clamping devices
Proteoglycans
Amino Acid Substitution
Invertebrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Whiteford, James R. ; Ko, Sunggeon ; Lee, Weon Tae ; Couchman, John R. / Structural and cell adhesion properties of zebrafish syndecan-4 are shared with higher vertebrates. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 43. pp. 29322-29330.
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Structural and cell adhesion properties of zebrafish syndecan-4 are shared with higher vertebrates. / Whiteford, James R.; Ko, Sunggeon; Lee, Weon Tae; Couchman, John R.

In: Journal of Biological Chemistry, Vol. 283, No. 43, 24.10.2008, p. 29322-29330.

Research output: Contribution to journalArticle

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