ZMBH J.Bericht 2000 - Zentrum für Molekulare Biologie der ...

Then, A. R., Berger, J., Schwarz, H., and Mayinger, P.
(2000). Sac1p regulates yeast cell wall organization in
a signaling pathway that is functionally related to the
Slt2p MAP kinase cascade. (in press).
THESES
Diploma
Grimm, O. (1999). Isolation and partial characterization
of proteins interacting with SRP-receptor.
Schlecker, T. (1999). Einfluß der intrazellulären Lokalisation
von Sac1p auf die Regulation des mikro–
somalen ATP-Transports.
Dissertations
Gruß, O. (1998). Regulation der Translokation neusyn–
thetisierter Polypeptide über die Membran des rauhen
endoplasmatischen Retikulums.
Then, A. (1999). Identifizierung von Faktoren die
funktionell mit dem Sac1p Protein in Saccharomyces
cerevisiae interagieren.
STRUCTURE OF THE GROUP
E-mail: dobberstein@zmbh.uni-heidelberg.de
Group leader Dobberstein, Bernhard, Prof. Dr.
Research
associates Mayinger, Peter, Dr.
Seedorf, Matthias, Dr.
Postdoctoral
fellows Barrett, Jeannie, Dr.*
Hendriks, Robertus, Dr.*
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Hölscher, Christina, Dr.
Kipp, Bettina, Dr.*
Martoglio, Bruno, Dr.*
Owens, Sue, Dr.*
Pool, Martin, Dr.
Wang, Lin, Dr.*
Ph.D. students Frey, Steffen,*
Fröschke, Marc
Gruß, Oliver*
Konrad, Gerlinde*
Then, Angela
Diploma students Grimm, Oliver*
Schlecker, Tanja*
Techn. assistants Bach, Ute
Meese, Klaus
*part of the time reported
Dirk Görlich
Nucleocytoplasmic Transport
The need for nuclear transport
The nuclear envelope (NE) divides eukaryotic cells
into a nuclear and a cytoplasmic compartment and
thereby necessitates exchange between nucleus and
cytoplasm. Not only must all nuclear proteins, such as
histones and transcription factors, be imported from
the cytoplasm, but also, tRNA, rRNA and mRNA are
synthesised by transcription in the nucleus and need to
be exported to the cytoplasm where they function in
translation. Nuclear-cytoplasmic transport constitutes
a tremendous activity that requires considerable cellular
resources and involves probably > 100 different
and often very abundant proteins. However, these
expenses pay off as indicated by the fact that only
eukaryotes evolved into complex multicellular organisms.
One can think of several reasons why a cell
nucleus is required for such cellular complexity. First,
the containment of the genome in a specialised organelle
certainly improves genetic stability and allows
eukaryotes to handle more genetic information than
prokaryotes. Second, this compartmentation permits
key cellular events to be regulated at a level that
is unavailable to prokaryotes, e.g. by controlling the
access of transcriptional regulators to chromatin. A
further reason is the composition of typical eukaryotic
genes from exons and introns, which requires primary
transcripts to be spliced before translation may occur.
Translation of unspliced pre-mRNAs would produce
proteins that are not only non-functional but which
may potentially act as dominant-negative inhibitors.
The confinement of transcription and translation to
distinct compartments can therefore be considered a
good solution to avoid this problem.
Importin beta-like transport receptors
P. Schwarzmaier, U. Kutay, G. Lipowsky, F. Paraskeva,
S. Jäckel, K. Ribbeck, K. Dean, in collaboration
with E. Hartmann (Univ. Göttingen), R. Kraft and
S. Kostka (MDC, Berlin)
Nuclear-cytoplasmic transport proceeds through
nuclear pore complexes (NPCs) which allow passive
diffusion of small molecules up to 20-40kD and also
active, i.e., carrier-mediated transport of macromolecules.
This active transport can occur along a great
variety of distinct pathways, many of which are mediated
by transport receptors that are at least distantly
related to importin β. Transport receptors that confer
import into the nucleus are referred to as importins,
while export mediators are called exportins.
A major objective of our laboratory has been to obtain
a detailed and comprehensive overview of the various
nuclear transport pathways. To identify novel transport
receptors, we have employed a biochemical approach
combined with data base searches and have so far
arrived at 22 mammalian members of the importin β
superfamily. In the following, we will briefly summarise
some of our recent insights in the mechanistic
principles of transport receptor function and elaborate
some nuclear transport pathways in more detail.
Mechanistic principles of transport receptor
function
Importins or exportins are capable of mediating multiple
rounds of transport, which requires them to shuttle
continuously between nucleus and cytoplasm. A given
transport cycle, however, can only be productive if
the corresponding transport receptor carries cargo in
one direction only and returns „empty“ to the original
compartment. This asymmetry in the transport cycles
can be explained by the RanGTP-gradient model. Ran
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