Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2.
FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals through a ternary complex with high-affinity FGF receptors and heparan sulfate proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is independent of the classical secretory pathway, remains elusive. To test the hypothesis that FGF-2 secretion is linked to its cell-surface ligands, we studied FGF-2 release using mutants defective for HSPG binding and cells with impaired HSPG biosynthesis. Here, we report that a functional interaction between FGF-2 and HSPGs is required for net export of FGF-2 from mammalian cells. FGF-2 release requires extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form a molecular trap that drives FGF-2 translocation across the plasma membrane.
Zehe
Christoph
C
Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Engling
André
A
Wegehingel
Sabine
S
Schäfer
Tobias
T
Nickel
Walter
W
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D018920:Coculture Techniques; D006224:Cricetinae; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D019812:Heparan Sulfate Proteoglycans; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2