Director, Human Technophile, Milan, ITALY
Role of mechanics from endosome function to liver disease
Host: G. Del Sal
Bio:
Our group is interested in understanding biological systems from the molecular to the
cellular, from cellular to `tissue and organism scale. In this multi-scale perspective, we have
been exploring the role of mechanical forces. Rab GTPases are key components for the
biogenesis, transport and functions of cellular membrane organelles. Among Rab effector
proteins, membrane tethers provide the first level of specificity in the recognition of a vesicle
by its target compartment. EEA1 is a long dimeric coiled-coil tether that, upon binding Rab5
to its N-terminus, undergoes a conformational change, from extended to a more flexible
“collapsed” state, giving rise to an effective mechanical force. Mechanical forces are also
important at the level of tissue organization. In the liver, hepatocytes are uniquely polarized
cells at the interface of sinusoidal endothelial and bile canaliculi that transport blood and bile,
respectively. In contrast to simple epithelia, where the cells have a single apical surface facing
the lumen of organs, hepatocytes have multiple apical and basal domains, i.e. a multipolar
(biaxial) organization. Their apical surface grows anisotropically to create the narrow tubes of
the bile canaliculi and their three-dimensional 3D organization. Such anisotropic growth is due
to the generation of apical protrusions, termed apical bulkheads, that connect the opposed
apical surfaces of hepatocytes. The apical bulkheads are under tension and, thus, are structural
elements which can provide mechanical stability to the elongating bile canalicular lumen
under inner pressure. We aim to elucidate the molecular mechanisms underlying mechano-
sensing and -transduction in response to luminal pressure and regulating hepatocyte cell fate
International Seminar Programme
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