Ludger Johannes, Institut Curie, INSERM
SoMS, BABS and GSBE Cross-Faculty Seminar Series
Abstract: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. Our previous studies have allowed us to propose a novel hypothesis, termed GL-Lect hypothesis: nanodomain construction by GlycosphingoLipid-binding cellular or pathological Lectins induces membrane curvature changes and drives the formation of endocytic pits for the cellular uptake of glycosylated membrane proteins with critical roles in cell migration (CD44, alpha5beta1 integrin...), of pathogens (polyoma viruses, norovirus) or pathogenic factors (Shiga and cholera toxins). 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. Furthermore, we are identifying mechanisms by which the GL-Lect mechanism is acutely controlled at the plasma membrane. Finally, we study how GL-Lect domain construction at the plasma membrane programs the intracellular distribution of cargo molecules, notably via the retrograde transport route.
Bio:Ludger Johannes (PhD) is Research Director (DR1) at INSERM. His research aims at establishing fundamental concepts of endocytosis and intracellular trafficking. The Johannes group has made two major contributions in this context: the discovery of a membrane trafficking interface between early endosomes and the Golgi apparatus, and the demonstration that dynamic lectin-induced glycosphingolipid reorganization acts as a driving force for endocytic pit construction in clathrin-independent endocytosis. These studies have been published in journals including Cell, Nature, Nat Cell Biol, Dev Cell and J Cell Biol. He also aims at exploiting these discoveries for the development of innovative cancer therapy strategies. His basic studies have allowed him to validate the B-subunit of Shiga toxin as a "pilot" for the delivery of therapeutic compounds to precise intracellular locations of dendritic and tumor cells (10 patent families).
Date & Time: Wednesday 12 July at 4.00 pm followed by Happy Hour.
Venue: Lowy Cancer Research Centre, Level 4 seminar space Map