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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Stuart A Cain
  • Andrew K Baldwin
  • Yashithra Mahalingam
  • Bertrand Raynal
  • Thomas A Jowitt
  • C Adrian Shuttleworth
  • Couchman, John Robert
  • Cay M Kielty
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.
Original languageEnglish
JournalJournal of Biological Chemistry
Issue number40
Pages (from-to)27017-27
Number of pages10
Publication statusPublished - 2008

ID: 7691443