A mobile endocytic network connects clathrin-independent receptor endocytosis to recycling and promotes T cell activation

Ewoud B. Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R. Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P. B. Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukian, Katharina Gaus and Jérémie Rossy ()
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Ewoud B. Compeer: University of New South Wales
Felix Kraus: University of New South Wales
Manuela Ecker: University of New South Wales
Gregory Redpath: University of New South Wales
Mayan Amiezer: University of New South Wales
Nils Rother: University of New South Wales
Philip R. Nicovich: University of New South Wales
Natasha Kapoor-Kaushik: University of New South Wales
Qiji Deng: University of New South Wales
Guerric P. B. Samson: Biotechnology Institute Thurgau at the University of Konstanz
Zhengmin Yang: University of New South Wales
Jieqiong Lou: University of New South Wales
Michael Carnell: University of New South Wales
Haig Vartoukian: University of New South Wales
Katharina Gaus: University of New South Wales
Jérémie Rossy: University of New South Wales

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04088-w

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