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

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

doi:10.1038/s41467-018-04088-w

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

Compeer EB EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Kraus F EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Ecker M EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Redpath G EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Amiezer M EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Rother N EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Nicovich PR EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Kapoor-Kaushik N EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Deng Q EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Samson GPB Biotechnology Institute Thurgau at the University of Konstanz, 8280, Kreuzlingen, Switzerland.
Yang Z EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Lou J EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Carnell M Biomedical Imaging Facility, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Vartoukian H EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Gaus K EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia.
Rossy J EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, High St Gate 9, Sydney, NSW, 2052, Australia. jeremie.rossy@bitg.ch.

2018-04-25

Published in:

Nature communications. - 2018

English 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.

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