, Volume 20, Issue 4, pp 400–403 | Cite as

Die molekulare Entschlüsselung unkonventioneller Sekretionsmechanismen

  • Julia P. Steringer
  • Hans-Michael Müller
  • Walter NickelEmail author
Wissenschaft · Special: Zellbiologie Proteinsekretion


The vast majority of secretory proteins is characterized by N-terminal signal peptides that allow for co-translational translocation into the lumen of the endoplasmic reticulum, the initial compartment of the classical ER/Golgi-dependent secretory pathway. However, extracellular proteins with fundamental physiological functions in immune surveillance and tissue organization have been identified that lack signal peptides. The molecular mechanisms by which these unconventional secretory proteins reach the extracellular space are beginning to emerge.


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  1. [1]
    Muesch A, Hartmann E, Rohde K et al. (1990) A novel pathway for secretory proteins? Trends Biochem Sci 15:86–88PubMedCrossRefGoogle Scholar
  2. [2]
    Zhang M, Schekman R (2013) Cell biology. Unconventional secretion, unconventional solutions. Science 340:559–561Google Scholar
  3. [3]
    Engling A, Backhaus R, Stegmayer C et al. (2002) Biosynthetic FGF-2 is targeted to non-lipid raft microdomains following translocation to the extracellular surface of CHO cells. J Cell Sci 115:3619–3631PubMedCrossRefGoogle Scholar
  4. [4]
    Nickel W (2005) Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic 6:607–614PubMedCrossRefGoogle Scholar
  5. [5]
    Schäfer T, Zentgraf H, Zehe C et al. (2004) Unconventional secretion of fibroblast growth factor 2 is mediated by direct translocation across the plasma membrane of mammalian cells. J Biol Chem 279:6244–6251PubMedCrossRefGoogle Scholar
  6. [6]
    Backhaus R, Zehe C, Wegehingel S et al. (2004) Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding. J Cell Sci 117:1727–1736PubMedCrossRefGoogle Scholar
  7. [7]
    Nickel W, Seedorf M (2008) Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells. Annu Rev Cell Dev Biol 24:287–308PubMedCrossRefGoogle Scholar
  8. [8]
    Temmerman K, Ebert AD, Muller HM et al. (2008) A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2. Traffic 9:1204–1217PubMedCrossRefGoogle Scholar
  9. [9]
    Nickel W (2007) Unconventional secretion: an extracellular trap for export of fibroblast growth factor 2. J Cell Sci 120:2295–2299PubMedCrossRefGoogle Scholar
  10. [10]
    Zehe C, Engling A, Wegehingel S et al. (2006) Cellsurface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proc Natl Acad Sci USA 103:15479–15484PubMedCentralPubMedCrossRefGoogle Scholar
  11. [11]
    Ebert AD, Laussmann M, Wegehingel S et al. (2010) Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 11:813–826PubMedCrossRefGoogle Scholar
  12. [12]
    Nickel W, Rabouille C (2009) Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol 10:148–155PubMedCrossRefGoogle Scholar
  13. [13]
    Nickel W (2011) The unconventional secretory machinery of fibroblast growth factor 2. Traffic 12:799–805PubMedCrossRefGoogle Scholar
  14. [14]
    Steringer JP, Bleicken S, Andreas H et al. (2012) Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion. J Biol Chem 287:27659–27669PubMedCentralPubMedCrossRefGoogle Scholar
  15. [15]
    Rabouille C, Malhotra V, Nickel W (2012) Diversity in unconventional protein secretion. J Cell Sci 125:5251–5255PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Julia P. Steringer
    • 1
  • Hans-Michael Müller
    • 1
  • Walter Nickel
    • 1
    • 2
    Email author
  1. 1.Biochemie-Zentrum der Universität Heidelberg (BZH)HeidelbergGermany
  2. 2.Biochemie-Zentrum der Universität Heidelberg (BZH)Universität HeidelbergHeidelbergGermany

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