PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation.
Platelet-derived growth factor (PDGF) signaling is essential for processes involving cell motility and differentiation during embryonic development in a wide variety of organisms including the mouse, frog, zebrafish, and sea urchin. In early Xenopus laevis embryos, PDGF-AA provides guidance cues for the migration of anterior mesendoderm cells as they move across a fibronectin-rich extracellular matrix. The long form of PDGF-A includes a positively charged carboxyl-terminal retention motif that can interact with the extracellular matrix and heparan sulfate proteoglycans (HSPGs). In this study we demonstrate that PDGF-AA binds directly to fibronectin and that this association is greatly enhanced by heparin. The PDGF-AA-fibronectin binding occurs across a broad range of pHs (5.5-9), which is significant because the PDGF-guided migration of Xenopus mesendoderm cells occurs under basic extracellular conditions (pH 8.4). We further demonstrate that endogenous HSPG's are required for the PDGF-AA-guided mesendoderm movement, suggesting an in vivo role for HSPGs in mediating the interaction between PDGF-AA and fibronectin.
Smith
Erin M
EM
Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Mitsi
Maria
M
Nugent
Matthew A
MA
Symes
Karen
K
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D005775:Gastrula / Q000166:cytology*; D006497:Heparan Sulfate / Q000502:physiology*; D007150:Immunohistochemistry; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014981:Xenopus
D005353:Fibronectins; D006497:Heparan Sulfate; D010982:Platelet-Derived Growth Factor; D011133:Polysaccharide-Lyases; C075278:platelet-derived growth factor A; C021349:heparitinsulfate lyase