Abstract
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.
Highlights
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
We show that in activated T cells T cell receptor (TCR) is internalized through a clathrin-independent pathway into a mobile and long-lived endocytic network supported by flotillins, which controls its recycling to the immunological synapse
We observed that T cell receptor complex subunit ζ (TCRζ) was rapidly internalized, with most initially photoactivated molecules incorporated into vesicles within 20 s after photoactivation (Fig. 1b, c, and Supplementary Video 2)
Summary
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. We show that in activated T cells TCR is internalized through a clathrin-independent pathway into a mobile and long-lived endocytic network supported by flotillins, which controls its recycling to the immunological synapse.
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