title: Single Particle Tracking Reveals that EGFR Signaling Activity Is Amplified in Clathrin-Coated Pits.
abstract: Signaling from the epidermal growth factor receptor (EGFR) via phosphorylation on its C-terminal tyrosine residues requires self-association, which depends on the diffusional properties of the receptor and its density in the plasma membrane. Dimerization is a key event for EGFR activation, but the role of higher order clustering is unknown. We employed single particle tracking to relate the mobility and aggregation of EGFR to its signaling activity. EGFR mobility alternates between short-lived free, confined and immobile states. In the immobile state, EGFR tends to aggregate in clathrin-coated pits, which is further enhanced in a phosphorylation-dependent manner and does not require ligand binding. EGFR phosphorylation is further amplified by cross-phosphorylation in clathrin-coated pits. Because phosphorylated receptors can escape from the pits, local gradients of signaling active EGFR are formed. These results show that amplification of EGFR phosphorylation by receptor clustering in clathrin-coated pits supports signal activation at the plasma membrane.
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ibach
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Radon
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Márton
authors.initials: M
authors.lastname: Gelléri
authors.affiliation: Laboratory of Chemical Biology, Department of Biomedical Engineering, and Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Sonntag
authors.affiliation: Laboratory of Chemical Biology, Department of Biomedical Engineering, and Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Luc
authors.initials: L
authors.lastname: Brunsveld
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Philippe I H
authors.initials: PI
authors.lastname: Bastiaens
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Verveer
mesh_terms: D002966:Clathrin / Q000378:metabolism*; D016000:Cluster Analysis; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D002966:Clathrin; D008024:Ligands; D066246:ErbB Receptors