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Cell surface proteoglycans syndecan-1 and -4 bind overlapping but distinct sites in laminin α3 LG45 protein domain.

Carulli, Sonia, Beck, Konrad, Dayan, Guila, Boulesteix, Sophie, Lortat-Jacob, Hugues and Rousselle, Patricia 2012. Cell surface proteoglycans syndecan-1 and -4 bind overlapping but distinct sites in laminin α3 LG45 protein domain. The Journal of Biological Chemistry 287 (15) , pp. 12204-12216. 10.1074/jbc.M111.300061

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Keratinocyte migration during epidermal repair depends on interactions between cellular heparan sulfate proteoglycan receptors, syndecan-1 and -4, and the C-terminal globular domains (LG45) of the extracellular matrix protein laminin 332. This study investigates the molecular basis of the binding specificity of the syndecan-1 and -4 receptors expressed by human keratinocytes. We used site-directed mutagenesis to alter a recombinant LG45 protein by substituting the most critical basic residues with glutamine. All proteins were expressed in mammalian cells, purified, and characterized biochemically. We used in vitro binding assays, including surface plasmon resonance, to examine interactions between mutated LG45 and heparan sulfates, syndecan-1 and -4. We identify a major heparin binding domain on the outer edge of a β-strand of LG45 surrounded by a track of converging low affinity residues. This domain harbors distinctive syndecan-1 and -4 binding-specific sequences. This is the first study to demonstrate a binding specificity of two proteoglycans produced by a single cell type. In addition, we found that although syndecan-1 interacts exclusively through its glycosaminoglycan chains, syndecan-4 binding relies on both its core protein and its heparan sulfate chains. These results suggest that LG45 may trigger different signals toward keratinocytes depending on its interaction with syndecan-1 or -4.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QH Natural history > QH301 Biology
Uncontrolled Keywords: Basement Membrane; Cell Adhesion; Epidermis; Extracellular Matrix Proteins; Glycosaminoglycan; Heparan Sulfate; Laminin; Proteoglycan; Laminin 332; Syndecan
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Funders: Agence Nationale de la recherche ANR-08-PCVI-0031, Agence Nationale de la recherche ANR-09-EBIO-023, Association pour la Recherche sur le Cancer Grant 1128, Ligue Nationale Contre le Cancer
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Last Modified: 04 Jun 2017 03:36

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