title: Propranolol restricts the mobility of single EGF-receptors on the cell surface before their internalization.
abstract: The epidermal growth factor receptor is involved in morphogenesis, proliferation and cell migration. Its up-regulation during tumorigenesis makes this receptor an interesting therapeutic target. In the absence of the ligand, the inhibition of phosphatidic acid phosphohydrolase activity by propranolol treatment leads to internalization of empty/inactive receptors. The molecular events involved in this endocytosis remain unknown. Here, we quantified the effects of propranolol on the mobility of single quantum-dot labelled receptors before the actual internalization took place. The single receptors showed a clear stop-and-go motion; their diffusive tracks were continuously interrupted by sub-second stalling events, presumably caused by transient clustering. In the presence of propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates an increase in drag of the receptor. Atomic force microscopy measurements did not show an increase of the effective membrane tension, such that clustering of the receptor remains the likely mechanism for its reduced mobility. ii) The receptor got frequently stalled for longer periods of multiple seconds, which may signal the first step of the internalization process.
authors.affiliation: Center for Integrative Medicine and Innovative Science (CIMIS), Universidad Andres Bello, Santiago, Chile ; Centro para el Desarrollo de la Nanociencia y Nanotecnologia, Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Otero
authors.affiliation: III. Physikalisches Institut, Faculty of Physics, Georg-August Universität, Göttingen, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Linke
authors.affiliation: III. Physikalisches Institut, Faculty of Physics, Georg-August Universität, Göttingen, Germany ; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Sanchez
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina and Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Alfonso
authors.initials: A
authors.lastname: González
authors.affiliation: III. Physikalisches Institut, Faculty of Physics, Georg-August Universität, Göttingen, Germany ; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Iwan A T
authors.initials: IA
authors.lastname: Schaap
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011433:Propranolol / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D011433:Propranolol; C512478:EGFR protein, human; D066246:ErbB Receptors