Gustave Roussy Institute, Inserm U1170
Team "Endocytosis, Cytoskeleton and Cell Migration"
Non-conventional functions of clathrin-coated structures
The general objective of our lab is to understand the functions of clathrin-coated structures (CCSs) during the different steps of cancer development. CCSs recruit specific cell surface receptors and progressively shape the plasma membrane in receptor-containing vesicles that are released in the cytosol. This endocytosis machinery allows for nutrient uptake but also for the fine-tuned control of signaling pathways triggered by cell surface receptors. As a consequence, deregulation of endocytosis has been linked to many pathological situations, including cancers.
Tumor development is accompanied by dramatic changes in the mechanical characteristics of tissues. Also, when cancer cells invade the stroma to establish distant metastases, they migrate in an environment with different topological features than the tumor mass. However, it is not known how the physical parameters of the environment impact on CCSs and what are the consequences for the cell.
Our team addresses this general question by developing two main aims:
- How the tumoral environment regulate CCSs
- nHow CCSs help cell to migrate in complex environments
The originality of our approach is to consider that CCSs functions are not limited to endocytosis but that the receptor-clustering step that precedes internalization may have functional consequences on its own, by compartmentalizing the plasma membrane. Supporting this hypothesis, we recently showed that integrin clustering at CCSs controls cell adhesion to collagen fibers in an endocytosis-independent manner (Elkhatib et al. 2017 Science).
- Elkhatib et al. 2017 Tubular clathrin/AP-2 lattices pinch collagen fibers to support 3D cell migration Science
- Ly et al. 2016 αTAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities Sci Rep
- Boissan, Montagnac et al. 2014 Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling Science
- Montagnac et al. 2013 αTAT1 catalyses microtubule acetylation at clathrin-coated pits Nature
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