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MPI für Intelligente Systeme; Nachwuchsgruppe Garcia Sáez;
Abstract:
Fibroblast growth factor 2 (FGF2) is a critical mitogen with a central role in specific steps of tumor-induced angiogenesis. It is known to be secreted by unconventional means bypassing the ER/Golgi dependent secretory pathway. However,the mechanism of FGF2 membrane translocation into the extracellular space has remained elusive. Here we show that PI(4,5)P2 dependent membrane recruitment causes FGF2 to oligomerize which, in turn, triggers the formation of a lipidic membrane pore with a putative toroidal structure. This process is strongly upregulated by tyrosine phosphorylation of FGF2. Our findings explain key
requirements of FGF2 secretion from living cells and suggest a novel self-sustained mechanism of protein translocation across membranes with a lipidic
membrane pore being a transient translocation intermediate.
