Compeer EB Kraus F Ecker M Redpath G Amiezer M Rother N Nicovich PR Kapoor-Kaushik N Deng Q Samson GPB Yang Z Lou J Carnell M Vartoukian H Gaus K Rossy J 2018 Endocytosis of surface receptors and their polarized recycling back to the plasma membrane are central to many cellular processes, such as cell migration, cytokinesis, basolateral polarity of epithelial cells and T cell activation. Little is known about the mechanisms that control the organization of recycling endosomes and how they connect to receptor endocytosis. Here, we follow the endocytic journey of the T cell receptor (TCR), from internalization at the plasma membrane to recycling back to the immunological synapse. We show that TCR triggering leads to its rapid uptake through a clathrin-independent pathway. Immediately after internalization, TCR is incorporated into a mobile and long-lived endocytic network demarked by the membrane-organizing proteins flotillins. Although flotillins are not required for TCR internalization, they are necessary for its recycling to the immunological synapse. We further show that flotillins are essential for T cell activation, supporting TCR nanoscale organization and signaling. application/pdf https://sonar.ch/global/documents/279134 eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-018-04088-w info:eu-repo/semantics/altIdentifier/pmid/29686427 info:eu-repo/semantics/openAccess Nature communications. - 2018 Animals Cell Line, Tumor Cell Membrane Endocytosis Humans Immunological Synapses Lymphocyte Activation Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Primary Cell Culture Receptors, Antigen, T-Cell Signal Transduction T-Lymphocytes A mobile endocytic network connects clathrin-independent receptor endocytosis to recycling and promotes T cell activation. http://purl.org/coar/resource_type/c_6501