title: Cell adhesion defines the topology of endocytosis and signaling.
abstract: Preferred sites of endocytosis have been observed in various cell types, but whether they occur randomly or are linked to cellular cues is debated. Here, we quantified the sites of endocytosis of transferrin (Tfn) and epidermal growth factor (EGF) in cells whose adhesion geometry was defined by micropatterns. 3D probabilistic density maps revealed that Tfn was enriched in adhesive sites during uptake, whereas EGF endocytosis was restricted to the dorsal cellular surface. This spatial separation was not due to distributions of corresponding receptors but was regulated by uptake mechanisms. Asymmetric uptake of Tfn resulted from the enrichment of clathrin and adaptor protein 2 at adhesive areas. Asymmetry in EGF uptake was strongly dependent on the actin cytoskeleton and led to asymmetry in EGF receptor activation. Mild alteration of actin dynamics abolished asymmetry in EGF uptake and decreased EGF-induced downstream signaling, suggesting that cellular adhesion cues influence signal propagation. We propose that restriction of endocytosis at distinct sites allows cells to sense their environment in an "outside-in" mechanism.
authors.affiliation: Molecular Mechanisms of Intracellular Transport, Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique Institut Curie, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Grossier
authors.forename: Georgia
authors.initials: G
authors.lastname: Xouri
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Kristine
authors.initials: K
authors.lastname: Schauer
mesh_terms: D000199:Actins / Q000378:metabolism; D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008856:Microscopy, Fluorescence; D015398:Signal Transduction; D014168:Transferrin / Q000378:metabolism*
chemical_list: D000199:Actins; D033962:Adaptor Protein Complex 2; D002966:Clathrin; D014168:Transferrin; D004815:Epidermal Growth Factor