Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex.
Basic fibroblast growth factor (bFGF) modulates functions of a variety of cell types. Whereas bFGF is known to act extracellularly, the protein lacks a transient signal peptide. No defined mechanism for bFGF secretion has been characterized besides release from dead or injured cells. To study this problem we devised an experimental system to examine bFGF-mediated migration of isolated single cells. Under these conditions individual cells are not affected by bFGF derived from other cells. By this method we have previously shown that bFGF released by NIH 3T3 cells transfected with bFGF cDNA modulates migration in an autocrine manner. We have now examined the effects on cell motility of drugs or treatments known to affect various pathways of protein secretion. Drugs that block secretion via the endoplasmic reticulum (ER)-Golgi complex or via multidrug resistance proteins did not inhibit cell motility. Migration was enhanced by the calcium ionophore A23187, which stimulates exocytosis, and was inhibited by methylamine, serum-free, and low temperature (18 degrees C) conditions, which block endo- and exocytosis. The reversal of these effects by the concomitant addition of affinity-purified anti-bFGF IgG or recombinant bFGF showed that the alterations in cell migration were mediated by changes in bFGF externalization. Thus bFGF can be released via a mechanism of exocytosis independent of the ER-Golgi pathway.
Mignatti
P
P
Dipartimento di Genetica e Microbiologia, Università di Pavia, Italy.
Morimoto
T
T
Rifkin
D B
DB
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D006046:Gold; D006056:Golgi Apparatus / Q000502:physiology*; D051379:Mice; D021382:Protein Sorting Signals / Q000032:analysis* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D000001:Calcimycin; D006046:Gold