An intrinsic quality-control mechanism ensures unconventional secretion of fibroblast growth factor 2 in a folded conformation.

Fibroblast growth factor 2 (FGF2) is a proangiogenic mitogen that is secreted by an unconventional mechanism, which does not depend on a functional ER-Golgi system. FGF2 is first recruited to the inner leaflet of plasma membranes, in a process that is mediated by the phosphoinositide PtdIns(4,5)P(2). On the extracellular side, membrane-proximal FGF2-binding sites provided by heparan-sulfate proteoglycans are essential for trapping and accumulating FGF2 in the extracellular space.