Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions.
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions. / Cain, Stuart A; Baldwin, Andrew K; Mahalingam, Yashithra; Raynal, Bertrand; Jowitt, Thomas A; Shuttleworth, C Adrian; Couchman, John R; Kielty, Cay M.
In: Journal of Biological Chemistry, Vol. 283, No. 40, 2008, p. 27017-27.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions.
AU - Cain, Stuart A
AU - Baldwin, Andrew K
AU - Mahalingam, Yashithra
AU - Raynal, Bertrand
AU - Jowitt, Thomas A
AU - Shuttleworth, C Adrian
AU - Couchman, John R
AU - Kielty, Cay M
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M803373200
DO - 10.1074/jbc.M803373200
M3 - Journal article
C2 - 18669635
VL - 283
SP - 27017
EP - 27027
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 40
ER -
ID: 7691443