Cysteine-rich fibroblast growth factor receptor alters secretion and intracellular routing of fibroblast growth factor 3.
Expression of the cysteine-rich fibroblast growth factor (FGF) receptor (CFR) in COS-1 cells strongly inhibits the secretion of co-expressed FGF3. By using a column retention assay and affinity chromatography, we demonstrate that at physiological salt concentrations FGF3 binds with strong affinity to CFR in vivo and in vitro. Furthermore, to show that FGF3 binds to CFR in vivo, truncation mutants of CFR with changed subcellular distributions were shown to cause a similar redistribution of FGF3. Although CFR is a 150-kDa integral membrane glycoprotein that is primarily located in the Golgi apparatus, we show here that in COS-1 cells a substantial proportion of CFR is secreted. This is due to a carboxyl-terminal proteolytic cleavage that releases the intraluminal portion of the protein for secretion. However, the apparent size of the integral membrane and secreted CFR appears similar, since the loss of protein mass is balanced by a gain of complex carbohydrates. The released CFR is associated with the extracellular matrix through its affinity for glycosaminoglycans. These findings show that CFR can modulate the secretion of FGF3 and may control its biological activity by regulating its secretion.
Köhl
R
R
Ruhr-Universität Bochum, Medizinische Fakultät, Abteilung für Virologie, Universitätsstrasse 150, Gebäuole MA 6/130, D-44780 Bochum, Germany.
Antoine
M
M
Olwin
B B
BB
Dickson
C
C
Kiefer
P
P
D000818:Animals; D019556:COS Cells; D002645:Chickens; D005109:Extracellular Matrix / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors