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Membrane protrusion powers clathrin-independent endocytosis of interleukin-2 receptor
Authors:Cyril Basquin  Léa Ripoll  Eija Jokitalo  Jean‐Christophe Olivo‐Marin  Alexis Gautreau  Nathalie Sauvonnet
Affiliation:1. Unité de Biologie des Interactions Cellulaires, Institut Pasteur, Paris, France;2. CNRS UMR3691, Paris, France;3. Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland;4. Unité d'Analyse d'Images Biologiques, Institut Pasteur, Paris, France;5. Laboratoire de Biochimie, Unité Mixte de Recherche 7654 Ecole Polytechnique Centre, National de la Recherche Scientifique, Palaiseau, France
Abstract:Endocytosis controls many functions including nutrient uptake, cell division, migration and signal transduction. A clathrin- and caveolin-independent endocytosis pathway is used by important physiological cargos, including interleukin-2 receptors (IL-2R). However, this process lacks morphological and dynamic data. Our electron microscopy (EM) and tomography studies reveal that IL-2R-pits and vesicles are initiated at the base of protrusions. We identify the WAVE complex as a specific endocytic actor. The WAVE complex interacts with IL-2R, via a WAVE-interacting receptor sequence (WIRS) present in the receptor polypeptide, and allows for receptor clustering close to membrane protrusions. In addition, using total internal reflection fluorescent microscopy (TIRF) and automated analysis we demonstrate that two timely distinct bursts of actin polymerization are required during IL-2R uptake, promoted first by the WAVE complex and then by N-WASP. Finally, our data reveal that dynamin acts as a transition controller for the recruitment of Arp2/3 activators required for IL-2R endocytosis. Altogether, our work identifies the spatio-temporal specific role of factors initiating clathrin-independent endocytosis by a unique mechanism that does not depend on the deformation of a flat membrane, but rather on that of membrane protrusions.
Keywords:actin  cytokine receptor  dynamin  protrusion  wave regulatory complex
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