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  PI(4,5)P2 dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion

Steringer, J. P., Bleicken, S., Andreas, H., Zacherl, S., Laussmann, M., Temmerman, K., et al. (2012). PI(4,5)P2 dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion. Journal of Biological Chemistry, 287(33), 27659-27669. doi:10.1074/jbc.M112.381939.

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Genre: Zeitschriftenartikel
Alternativer Titel : J. Biol. Chem.

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 Urheber:
Steringer, J. P.1, Autor
Bleicken, S.2, Autor           
Andreas, H.1, Autor
Zacherl, S.1, Autor
Laussmann, M.1, Autor
Temmerman, K.1, Autor
Contreras, F. X.1, Autor
Bharat, T. A.1, Autor
Lechner, J.1, Autor
Muller, H. M.1, Autor
Briggs, J. A.1, Autor
García-Sáez, A. J.2, Autor           
Nickel, W.1, Autor
Affiliations:
1Heidelberg University Biochemistry Center, Germany, ou_persistent22              
2Max Planck Research Group Membrane Biophysics, Max Planck Institute for Intelligent Systems, Max Planck Society, ou_1497659              

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Schlagwörter: MPI für Intelligente Systeme; Nachwuchsgruppe Garcia Sáez;
 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 2012
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 625306
DOI: 10.1074/jbc.M112.381939
 Art des Abschluß: -

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Titel: Journal of Biological Chemistry
  Alternativer Titel : J. Biol. Chem.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 287 (33) Artikelnummer: - Start- / Endseite: 27659 - 27669 Identifikator: -