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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.

Original publication

DOI

10.1038/s41467-018-04088-w

Type

Journal article

Journal

Nat Commun

Publication Date

23/04/2018

Volume

9

Keywords

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