Cell adhesion defines the topology of endocytosis and signaling

The EMBO Journal
Jean-Philippe GrossierKristine Schauer

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.

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Citations

Feb 4, 2016·Cell Adhesion & Migration·Philipp J Albert, Ulrich S Schwarz
Apr 11, 2014·Bioarchitecture·Kristine Schauer, Bruno Goud
Jun 4, 2014·Reviews in Medical Virology·Kai ZhengYifei Wang
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Nov 16, 2018·Current Protocols in Cell Biology·Anahi CapmanyKristine Schauer
Mar 16, 2019·Journal of Cell Science·Anahi CapmanyKristine Schauer
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Nov 17, 2020·Frontiers in Bioengineering and Biotechnology·Santosh Phuyal, Francesco Baschieri

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