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J Biol Chem. 2008 Oct 3;283(40):27017-27. doi: 10.1074/jbc.M803373200. Epub 2008 Jul 31.

Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions.

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  • 1Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, United Kingdom.

Abstract

Fibrillin-1 N- and C-terminal heparin binding sites have been characterized. An unprocessed monomeric N-terminal fragment (PF1) induced a very high heparin binding response, indicating heparin-mediated multimerization. Using PF1 deletion and short fragments, a heparin binding site was localized within the domain encoded by exon 7 after the first hybrid domain. Rodent embryonic fibroblasts adhered to PF1 and deletion fragments, and, when cells were plated on fibrillin-1 or fibronectin Arg-Gly-Asp cell-binding fragments, cells showed heparin-dependent spreading and focal contact formation in response to soluble PF1. Within domains encoded by exons 59-62 near the fibrillin-1 C terminus are novel conformation-dependent high affinity heparin and tropoelastin binding sites. Heparin disrupted tropoelastin binding but did not disrupt N- and C-terminal fibrillin-1 interactions. Thus, fibrillin-1 N-terminal interactions with heparin/heparan sulfate directly influence cell behavior, whereas C-terminal interactions with heparin/heparan sulfate regulate elastin deposition. These data highlight how heparin/heparan sulfate controls fibrillin-1 interactions.

PMID:
18669635
DOI:
10.1074/jbc.M803373200
[PubMed - indexed for MEDLINE]
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