Keynote Conference - Interevent

Symp#6 Membrane Biology
Chair José Garcia Abreu
New Inhibitory Wnt/β-catenin Mechanisms Affecting Embryonic Head Formation
Jose Garcia Abreu, PhD.
Instituto de Ciencias Biomédicas – Universidade Federal do Rio Janeiro. Rio de Janeiro – Brazil.
The establishment of vertebrate embryonic axes involves a series of cellular and molecular events right after
fertilization. In the frog embryo the dorsal ventral axis relies on accumulation of dorsal beta-catenin which together
with Nieuwkoop center set the dorsal organizer, also known as Spemann Organizer. Upon the onset of gastrulation a
number of secreted factors act dorsally preventing dorsal fate from ventral signals. At the same time cells from the
prechordal plate endomesoderm secrete inhibitors of ventro-lateral Wnt signals setting up the antero-posterior axis.
Therefore, Wnt/beta-catenin signaling plays major role in the establishment and patterning of embryonic axis. Here,
we present a new Wnt-beta-catenin inhibitor, expressed in the Spemann Organizer which is essential for proper head
formation. We also present data on how cholestero-rich membrane microdomains interfere with the morphogentic
fields in the head organizer, the pre-chordal plate.
Support: FAPERJ, CNPQ and CAPES.
Membrane Dynamics and Mechanics of Signaling: Role of Caveolae
Sinha, B., D. Koster, R. Ruez, P. Gonnord, M. Bastiani, D. Abankwa, R.V. Stan, G. Butler-Browne, B. Vedie, L. Johannes,
N. Morone, R.G. Parton, G. Raposo, P. Sens, C. Lamaze, and P. Nassoy. 2011. Cells respond to mechanical stress by
rapid disassembly of caveolae. Cell. 144:402-13.
Nassoy, P., and Christophe Lamaze. Stressing caveolae new role in cell mechanics. Trends Cell Biol. in press
Institut Curie, Paris, France
The functions of caveolae, the characteristic plasma membrane invaginations, has long remained debated. The
particular abundance of caveolae in endothelial and muscle cells cells, which respectively experience shear stress and
stretching, led us to investigate the role of caveolae in membrane-mediated mechanical response. Acute mechanical
stress induced by osmotic swelling or by uniaxial stretching results in a rapid disappearance of caveolae, in a reduced
caveolin/Cavin1 interaction, and in an increase of free caveolins at the plasma membrane. Tether-pulling force
measurements in cells and in plasma membrane spheres demonstrate that caveola flattening and disassembly is the
primary actin- and ATP-independent cell response that buffers membrane tension surges during mechanical stress.
Conversely, stress release leads to complete caveola reassembly in an actin- and ATP-dependent process. We further
show that mechanosensing through caveolae in endothelial cells involves the Jak/Stat signaling pathway. Caveolae are
therefore mechanosensors and mechanotransducers which constitute a physiological membrane reservoir that quickly
accommodates sudden and acute mechanical stresses.
Studying Spatial Control of Exocytosis at the Nanoscale in Living Cells
Derek Toomre
Yale University School of Medicine, USA
Cells spatially control exocytosis to control a range of biological function – from cell division, migration, invasion and
the formation of specialized structures such as the primary cilium. Loss of this spatial-temporal control can lead to
diseases including cancer, diabetes, and polycystic kidney disease. This seminar will focus firstly on new superresolution
‘nanoscopes’ and their power to visualize subcellular processes with incredible detail. I will then show how
it to query and even optogenetically manipulate the very last steps of exocystosis, vesicle tethering and fusion. As case
studies, I will show how this approach has given new insight and lead to new concept in cytokinesis, cell migration, and
insulin-mediated trafficking of Glut4 in adipocytes. For examples, in adipocytes we see two membrane trafficking
pathways to the surface and a regulation by insulin on the expansion of the fusion pore. Challenges and potentials of
these new nanoscopes, with special emphasis to membrane traffic, will be discussed.
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