Copy Link
Add to Bookmark
Report
dictyNews Volume 42 Number 11
dictyNews
Electronic Edition
Volume 42, number 11
April 15, 2016
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to dicty@northwestern.edu
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
Back issues of dictyNews, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.
Follow dictyBase on twitter:
http://twitter.com/dictybase
=========
Abstracts
=========
Heterotrimeric G protein shuttling via Gip1 extends the dynamic
range of eukaryotic chemotaxis
Yoichiro Kamimura Yukihiro Miyanaga and Masahiro Ueda
Laboratory for Cell Signaling Dynamics, Quantitative Biology
Center (QBiC), RIKEN, Suita, Osaka, 565-0874, Japan.
Laboratory for Single Molecular Biology, Department of Biological
Sciences, Graduate School of Science, Osaka University, Toyonaka,
Osaka, 560-0043, Japan.
Proc. Natl. Acad. Sci. USA , in press.
Chemotactic eukaryote cells can sense chemical gradients over
a wide range of concentrations via heterotrimeric G-protein
signaling; however, the underlying wide-range sensing mechanisms
are only partially understood. Here we report that a novel
regulator of G proteins, G protein-interacting protein 1 (Gip1),
is essential for extending the chemotactic range of Dictyostelium
cells. Genetic disruption of Gip1 caused severe defects in gradient
sensing and directed cell migration at high but not low
concentrations of chemoattractant. Also, Gip1 was found to bind
and sequester G proteins in cytosolic pools. Receptor activation
induced G-protein translocation to the plasma membrane from the
cytosol in a Gip1-dependent manner, causing a biased redistribution
of G protein on the membrane along a chemoattractant gradient.
These findings suggest that Gip1 regulates G-protein shuttling
between the cytosol and the membrane to ensure the availability
and biased redistribution of G protein on the membrane for receptor-
mediated chemotactic signaling. This mechanism offers an
explanation for the wide-range sensing seen in eukaryotic
chemotaxis.
submitted by: Masahiro Ueda [masahiroueda@fbs.osaka-u.ac.jp]
———————————————————————————————————————
Mutant p97 exhibits species-specific changes of its ATPase
activity and compromises the UBXD9-mediated monomerisation
of p97 hexamers
Ramesh Rijal, Khalid Arhzaouy, Karl-Heinz Strucksberg,
Megan Cross, Andreas Hofmann, Rolf Schroeder, Christoph S.
Clemen, Ludwig Eichinger
Eur. J. Cell Biol., in press
p97 (VCP) is a homo-hexameric triple-A ATPase that exerts a plethora
of cellular processes. Heterozygous missense mu-tations of p97 cause
at least five human neurodegenerative disorders. However, the
specific molecular consequences of p97 mutations are hitherto widely
unknown. Our in silico structural models of human and Dictyostelium
p97 showed that the disease-causing R93C, R155H, and R155C as well
as R154C, E219K, R154C/E219K mutations of human and Dic-tyostelium
p97, respectively, are surface exposed amino acid residues. In-gel p97
ATPase activity measurements of p97 monomers and hexamers revealed
significant mutation- and species-specific differences. While all
human p97 mutations led to an increase in ATPase activity, no changes
could be detected for the Dictyostelium R154C mutant, which is
orthol-ogous to human R155C. The E219K mutation led to an almost
complete loss of activity, which was partially recuperated in the
R154C/E219K double-mutant indicating p97 inter-domain communication.
By means of co-immunoprecipitation experiments we identified an
UBX-domain containing Dictyostelium protein as a novel p97 interaction
partner. We cate-gorized all UBX-domain containing Dictyostelium
proteins and named the interaction partner UBXD9. Pull-down assays and
surface plasmon resonance analyses of Dictyostelium UBXD9 or the human
orthologue TUG/ASPL/UBXD9 demon-strated direct interactions with p97
as well as species-, mutation- and ATP-dependent differences in the
binding affinities. Sucrose density gradients revealed that both human
and Dictyostelium UBXD9 proteins very efficiently disassembled wild-type,
but to a lesser extent mutant p97 hexamers into monomers. Our results
are consistent with a scenario in which p97 point mutations lead to
differences in enzymatic activities and molecular interactions, which in
the long-term result in a late-onset and progressive multisystem disease.
submitted by: Ludwig Eichinger [ludwig.eichinger@uni-koeln.de]
==============================================================
[End dictyNews, volume 42, number 11]
