Biochemie-Zentrum der Universität Heidelberg (BZH)

Christian Ungermann
Goal
Our group is interested in the mechanism of
organelle biogenesis membrane fusion within
the endolysosomal system. We use the vacu-
ole of the yeast Saccharomyces cerevisae as
a model system to study the role of tethering
factors, SNAREs and their regulators in an
organelle fusion reaction. Our work revealed
that endosome-vacuole biogenesis is deter-
mined by two homolgous tethering factors,
called CORVET and HOPS. A second focus of
the lab is the analysis of protein palmitoyla-
tion in membrane fusion.
Background
Organelles of the secretory and the endocytic
pathway are connected by vesicles that transport
proteins and lipids. Vesicles are formed on a donor
compartment with the help of coat proteins
and deliver their cargo upon fusion with the target
organelle (Fig. 1). Between endosome and lysosome,
transport also occurs by organelle maturation
rather than vesicular transport (Ungermann
and Langosch, 2005).
The yeast vacuole represents a perfect system
to study membrane fusion and biogenesis. Yeast
vacuoles are dynamic organelles that undergo fission
and fusion in response to osmotic changes,
36 Christian Ungermann
1996 PhD, University of Munich, Germany
1996-1999 Post-doctoral research fellow with Prof. William Wickner,
Dartmouth Medical School, Hanover, NH, U.S.A.
2002 EMBO Young Investigator award
2003 Appointment as university lecturer (venia legendi in
Biochemistry), Medical Faculty, University of Heidelberg,
1999-2005 Group leader at the Biochemie-Zentrum der Universität
Heidelberg (BZH), Germany
Since 2006 Full Professor at the Department of Biology, University of
Osnabrück, Germany
Vacuole biogenesis and protein palmitoylation
and can be monitored in vitro and in vivo. Fusion
of endosomes and vacuoles depends on the initial
membrane contact mediated by Rab GTPases
and tethering factors (at the endosome CORVET,
at the vacuole HOPS) and SNAREs, which drive
lipid-bilayer mixing.
Research Highlights
Within the last three years the lab shifted its focus
towards tethering factors and their role in endolysosomal
biogenesis. We identified a kinase
(Yck3) that modifies a subunit of the vacuolar
HOPS complex and regulates fusion (LaGrassa
et al., 2005), and established methods to isolate
the endosomal and vacuolar tethering complexes
(Fig. 2; Peplowska et al., 2007).
The novel endosomal CORVET complex and the
HOPS complex share four subunits, suggesting
that they can interconvert – an issue that we are
presently focussing on.
Most SNAREs are membrane proteins with a
C-terminal transmembrane domain, followed
by a coiled-coil/SNARE domain and a variable
N-terminal domain (NTD). In collaboration with
Dieter Langosch (TU Munich), we could show
that SNARE dimerization is critical for the hemifusion
to fusion transition (Hofmann et al., 2006).
The function of this dimerization is still unclear.