Ludger Johannes, PhD - "Glycolipid-dependent and lectin-driven construction of endocytic pits: The GL-Lect hypothesis"
Oct 26, 2016
from 02:30 PM to 04:00 PM
|Where||Tigem Auditorium "Vesuvius"|
|Contact Name||Carmine Settembre e Antonella De Matteis|
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Several endocytic processes do not require the activity of clathrin, and it has been a major
question in membrane biology to know how the plasma membrane is bent and cargo proteins are
sorted in these cases. In previous studies we found that nanodomain construction by
glycosphingolipid-binding lectin parts of toxins (e.g. Shiga and cholera toxins) or polyoma
viruses (e.g. SV40) induces membrane curvature changes and drives the formation of endocytic
pits for the cellular uptake of these pathogens or pathogenic factors (Nature 450, 670-675; NCB
12, 11-18). We could show that actin polymerization on Shiga toxin-induced endocytic tubules is
sufficient to trigger scission in a process that requires domain boundary forces (Cell 140, 540-
553). We are now analyzing how cortical actin dynamics contributes to the clustering of
glycosphingolipid-lectin complexes on active membranes, thereby facilitating the nucleation of
endocytic tubules exploiting fluctuation forces that had not been linked before to endocytosis.
Another important aspect of our studies concerns the recognition of lectin-induced highly bent
endocytic membrane invaginations by BAR domain proteins (Nature 517, 493), and the targeting
to and fusion with endosomes of correspondingly generated endocytic carriers (JCS 128, 2891).
Finally, we have identified a cellular lectin, galectin-3, that like the pathogenic lectins mentioned
above is capable of inducting the formation of narrow membrane invaginations in interaction
with glycosphingolipids (NCB 16, 595). Galectin-3 is required for the formation of clathrinindependent
carriers via which cargo proteins such as CD44 and a5b1 integrin are internalized
in to cells. Very recently, we have discovered that a5b1 integrin follows the retrograde transport
route from the plasma membrane back to the Golgi, and that this trafficking pathway is required
for the polarized distribution of the protein to the leading edge of migratory cells (NCB 18, 54).
These different elements will be discussed in the context of molecular hypothesis — termed GLLect
hypothesis — on how pathogenic or cellular lectins would drive the glycosphingolipiddependent
construction of endocytic pits.