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

Abstract

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°C) conditions, which block endoand 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. © 1992 Wiley‐Liss, Inc.

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…Both low and high molecular weight FGF2 isoforms show angiogenic activity [63]. At variance with other FGFs, FGF2 isoforms lack a leader sequence for secretion and are released in limited amounts by an alternative secretion pathway [64] or via membrane vesicle shedding [65]. Experimental evidences point to different functions of FGF2 isoforms in transfected endothelial cells [66], possibly related to differences in their subcellular localization and release.…”

Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium

“…11,12 The bFGF secretion pathway is unconventional because agents that disrupt the ER-Golgi apparatus and the multidrug resistance pathway do not inhibit the release of bFGF. 13 Proposed mechanisms by which bFGF is released from viable cells include exocytosis, 13 mild cell damage in response to stress, 10 receptor-mediated secretion 14 and a carrier (chaperone) protein. 15 Once outside the cell, heparan sulfate proteoglycans stabilize and protect bFGF from inactivation and function as low-affinity receptors that sequester bFGF and facilitate its interaction with highaffinity signaling receptors on the cell surface.…”

let-756, a C. elegans fgf essential for worm development

“…FGF1 and 2 are synthesized in the cytosol and are released by a mechanism independent of the ER-Golgi secretory pathway (Mignatti et al, 1992). Although FGF9 lacks a cleavable amino terminal signal, it is glycosylated and e ciently secreted from various cell lines, presumably via the ER-Golgi pathway (Miyamoto et al, 1993).…”