of the Max - MDC

Regulation of Nuclear
Transport Processes
Structure of the Group
Group Leader
Katrin Stade
Graduate and Undergraduate Students
Anja Neuber
Katrin Stade
(Helmholtz Fellow)
The transport of macromolecules between the nucleus and cytoplasm is a major cellular activity with respect to
both, the number of particles involved and energy consumption. Complex processes such as signal transduction
and cell cycle progression which also rely on nuclear transport reactions are tightly regulated at this level to occur
efficiently and in a coordinated fashion. Not unexpectedly, mutations in components of the nuclear transport
machinery result in deregulation of these processes and may ultimately lead to the development of severe human
disease as for example cancer, primary billiary cirrhosis and triple A syndrome.
Post-translational modifications such as phosphorylation are well known to control nuclear transport processes.
More recently, a rather novel protein modification system has been proposed to play a role in nucleocytoplasmic
trafficking. The ubiquitin-like small modifier SUMO which previously had been shown to play an important role in
transcriptional repression, chromosome segregation and DNA repair was also recognized as a key player for one particular
nuclear protein import pathway.
By the use of a genetic screen in the buddding yeast
Saccharomyces cerevisiae, we have recently identified several
novel factors involved in nuclear transport reactions and
gene silencing. Using in vivo experiments as well as in vitro
assays, we are currently studying these genes in more detail
and wish to elucidate the functional implications of SUMO
modification for the corresponding proteins.
Another research interest of the lab is the karyopherin
Crm1/Xpo1 which in virally infected eukaryotic cells is
responsible for the nuclear export of the HIV pre-messenger
RNA particle. The budding yeast orthologue Xpo1 was found
to export reporter proteins containing a nuclear export signal
and several classes of cellular RNA. Since then Xpo1 has
been characterized in greater detail, but many questions
still remain unsolved: what are the major cellular export
substrates for this exportin and how are they transported to
the cytoplasm? Does Xpo1 like other components of the
nuclear transport machinery play an additional role in chromosome
segregation during mitosis and how is this
achieved? We are currently addressing these questions by
the use of genetic strategies as well as biochemical methods
in the budding yeast Saccharomyces cerevisae.
Genetic analysis of a yeast strain
A diploid yeast cell was induced to sporulate by depletion of nitrogen from the growth
medium. After meiosis, four haploid spores form which are contained in a so-called
ascus. Following enzymatic digestion of the ascus wall, the four spores are separated
manually under the microscope and are put onto a petri dish with growth medium. Each
column on the petri dish represents a complete tetrad with four individual spores.
Selected Publications
Pannek, A and Katrin Stade, K. (2006) Nuclear Import and
Export. Encyclopedic Reference of Genomics and Proteomics in
Molecular Medicine Ganten, D. and Ruckpaul, K. (eds) Springer
Verlag, Heidelberg, New York.
Cronshaw, JM and Matunis, M. (2004) The nuclear pore complex:
disease associations and functional correlations. Trends in
Endocrinology and Metabolism 15, 34-39.
Stade, K, Vogel, F, Schwienhorst, I, Meusser, B, Volkwein, C,
Nentwig, B, Dohmen, RJ and Sommer, T. (2002). A lack of SUMO
conjugation affects cNLS-dependent nuclear protein import in
yeast J. Biol. Chem. 277, 49554-49561.
100 Cancer Research