Blanche Schwappach
Dr. rer. nat. 1996 at the Center for Molecular Neurobiology
in Hamburg. Postdoctoral work at the University of California,
San Francisco. Group leader at the ZMBH since 2000.
Assembly and trafficking of ion channels
Previous and Current research
Each cell type possesses an exquisitely regulated set of plasma
membrane proteins. It is essential that these be expressed in
their properly folded and correctly assembled form in appropriate
numbers at the cell surface. This is particularly true for ion
channels since a very small number of channel proteins can have
dramatic effects on the electrical excitability of a cell. Almost
all ion channels are multimeric protein complexes and the respective
composition of the complex can greatly affect its functional
properties. How is assembly and precise stoichiometry of ion
channels controlled? What determines the subcellullar localization
of ion channel subunits at different stages of assembly? We have
started to address some of these questions using the ATP-sensitive
potassium channel as a model system (KATP channels couple the
metabolic state of the cell to membrane excitability). We found
that the primary quality control mechanism during KATP assembly
involved the exposure of an ER localization signal present in
cytosolic domains of each subunit.
We wish to understand the arginine-based ER localization signals
that we identified in KATP channels as well as the cellular machinery
that recognizes them. To this end we have embarked on a random
screen of ER trafficking motifs in mammalian cells. The screen
is based on retroviral gene transfer and flow cytometry. Eventually,
we would like to ask how the cell regulates the number of channels
at the cell surface. How are the relevant quality control and
trafficking processes regulated in response to environmental
change?
Projects for graduate students
Characterization of proteins that interact with certain ion
channel subunits in mammalian cells, mapping of interaction domains,
regulation of interaction
Screening of expression libraries in mammalian cells to identify
proteins that regulate surface expression of ion channel complexes
Contact:
Blanche Schwappach
ZMBH, Universitaet Heidelberg,
Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany
phone +49-6221-54 68 98
fax +49-6221-54 58 94
email b.schwappach@zmbh.uni-heidelberg.de
http://www.zmbh.uni-heidelberg.de/Schwappach/
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Selected publications
- Lloyd S.E., Pearce S.H.S., Fisher S.E., Steinmeyer K., Schwappach
B., Scheinman S.J., Harding B., Bolino, A., Devoto M., Goodyer
P., Rigden S.P.A., Wrong O., Jentsch T.J., Craig I.W., and Thakker
R.V. (1996). A common molecular basis for three inherited kidney
stone diseases. Nature, 379, 445-449.
Hechenberger M., Schwappach B., Fischer W.N., Frommer W.B., Jentsch
T.J., and Steinmeyer K. (1996). A family of putative chloride
channels from Arabidopsis and functional complementation of a
yeast strain with a CLC gene disruption. J. Biol. Chem.,
271, 3363233638.
Schwappach B., Stobrawa S., Hechenberger M., Steinmeyer K., and
Jentsch T.J. (1998). Golgi Localization and functionally important
domains in the NH2 and COOH terminus of the yeast CLC putative
chloride channel Gef1p. J. Biol. Chem., 273, 1511015118.
Zerangue N. *, Schwappach B. *, Jan Y.N., and Jan L.Y. (1999,
*these authors contributed equally). A new ER trafficking signal
regulates the subunit stoichiometry of plasma membrane KATP channels,
Neuron 22, 537-548.
Schwappach, B. *, Zerangue, N. * Jan Y.N., and Jan L.Y. (2000),
*these authors contributed equally). Molecular basis for KATP
assembly: transmembrane interactions mediate association of a
K+ channel with an ABC transporter. Neuron 26, 155-167.
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