Sweet cues: How heparan sulfate modification of fibronectin enables growth factor guided migration of embryonic cells.
Growth factors regulate a diverse array of cellular functions including proliferation, survival, movement, and the ability to do this often involves interactions with the extracellular matrix (ECM) and particularly heparan sulfate proteoglycans (HSPGs). HSPGs have been shown to sequester growth factors, and to act as growth factor co-receptors or receptors themselves. Recent studies, however, have revealed a new role for HSPGs in mediating the interactions of growth factors with the ECM. Specifically, heparan sulfate has been shown to modulate fibronectin structure to reveal previously masked growth factor binding sites. In vivo, this mechanism appears to control the guidance of migrating cells during embryonic development as HSPG-modification of fibronectin enables direct platelet derived growth factor-fibronectin interactions necessary for this process. A model based on this observation is discussed here as well as the possibility that other growth factors/morphogens utilize similar mechanisms involving fibronectin or additional ECM proteins.
Symes
Karen
K
Department of Biochemistry, Boston University School of Medicine; Boston, MA, USA. symes@bu.edu
Smith
Erin M
EM
Mitsi
Maria
M
Nugent
Matthew A
MA
D000818:Animals; D002465:Cell Movement; D047108:Embryonic Development; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A