Walter Nickel
Heidelberg University Biochemistry Center
- 1994 Graduation (PhD), University of Göttingen, Germany
- 1994-1997 Post-doctoral research fellow
Institute for Biochemistry I, Heidelberg University, Germany
1997-2000 Post-doctoral research fellow
Memorial Sloan-Kettering Cancer Center, New York, U.S.A.
- 2001 venia legendi in Biochemistry, Heidelberg University,
Germany
- 2001-Group Leader at Heidelberg University Biochemistry Center,
Germany
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Non-classical Mechanisms of Eukaryotic Protein Secretion
Proteins destined for the classical pathway of secretion (e.g.
serum proteins such as immunoglobulins) typically contain an
N-terminal signal peptide that mediates translocation into the
lumen of the endoplasmic reticulum followed by ER/Golgi-dependent
transport to the cell surface. By contrast, a growing number
of proteins such as angiogenic growth factors (Fibroblast Growth
Factor (FGF) 1 and 2), lectins of the extracellular matrix (family
of the galectins), infection-related cell surface markers of
Leishmania parasites (HASP family), inflammatory cytokines such
as interleukin 1b as well as viral proteins such as Herpes simplex
tegument protein VP22 lack a signal peptide yet they are secreted
from eukaryotic cells. Consistently, these secretory proteins
do not localize to classical secretory organelles such as the
endoplasmic reticulum and the Golgi apparatus and have been shown
not to contain ER/Golgi-specific posttranslational modifications
such as glycosylation. Importantly, inhibitors of the classical
secretory pathway such as brefeldin A do not interfere with secretion
of these proteins. Thus, unconventional mechanisms of protein
secretion have been postulated, however, the machineries that
mediate these processes remain to be identified in molecular
terms.
Based on both in vivo and in vitro systems functionally reconstituting
the transport processes described we are currently analyzing
the molecular components that mediate export of FGF-2, galectin-1
and HASPB. Moreover, we make use of these systems in order to
identify small molecular weight molecules that interfere with
unconventional protein secretion pathways. Such molecules have
great potential to serve as lead compounds for the development
of for example anti-angiogenic drugs.
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Selected Publications
T. Schäfer, H. Zentgraf, C. Zehe, B. Brügger, J.
Bernhagen, and W. Nickel (2004) Unconventional Protein Secretion:
Direct Translocation of Fibroblast Growth Factor 2 Across the
Plasma Membrane of Mammalian Cells. J. Biol. Chem., in press
R. Backhaus, C. Zehe, S. Wegehingel, A. Kehlenbach, B. Schwappach,
and W. Nickel (2004) Unconventional Protein Secretion: Membrane
Translocation of FGF-2 Does Not Require Protein Unfolding. J.
Cell Sci., in press
O. Flieger, A. Engling, R. Bucala, H. Lue, W. Nickel, and
J. Bernhagen (2003) Regulated secretion of macrophage migration
inhibitory factor is mediated by a nonclassical pathway involving
an ABC transporter. FEBS Lett. 551:78-86
W. Nickel (2003) The Mystery of Non-classical Protein Secretion:
A Current View on Cargo Proteins and Po-tential Export Routes.
Eur. J. Biochem. 270:2109-2119
C. Seelenmeyer, S. Wegehingel, J. Lechner, and W. Nickel (2003)
The tumor antigen CA125 represents a novel counter receptor for
galectin-1.
J. Cell Sci. 116:1305-1318
A. Engling, R. Backhaus, C. Stegmayer, C. Zehe, C. Seelenmeyer,
A. Kehlenbach, B. Schwappach, S. Wegehingel, and W. Nickel (2002)
Biosynthetic FGF-2 is Targeted to Non-Lipid Raft Microdomains
Following Translocation to the Extracellular Surface of CHO cells.
J. Cell Sci. 115:3619-3631
Contact:
PD Dr. Walter Nickel
Biochemie-Zentrum Heidelberg,
Im Neuenheimer Feld 328
D-69120 Heidelberg, Germany
phone +49-6221-54 54 25 (office), -54 54 27 (lab)
fax +49-6221-54 43 66
email: walter.nickel@urz.uni-heidelberg.de
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